218 results on '"Couté Y"'
Search Results
2. SIN3 acts in distinct complexes to regulate the germline transcriptional program in C. elegans
- Author
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Robert, V. J., primary, Caron, M., additional, Gely, L., additional, Adrait, A., additional, Pakulska, V., additional, Couté, Y., additional, Chevalier, M., additional, Riedel, C. G., additional, Bedet, C., additional, and Palladino, F., additional
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- 2023
- Full Text
- View/download PDF
3. The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages
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ten Hoeve, Arne L., Braun, L., Rodriguez, Matias E., Olivera, Gabriela C., Bougdour, A., Belmudes, L., Couté, Y., Saeij, J. P. J., Hakimi, M.-A., Barragan, Antonio, ten Hoeve, Arne L., Braun, L., Rodriguez, Matias E., Olivera, Gabriela C., Bougdour, A., Belmudes, L., Couté, Y., Saeij, J. P. J., Hakimi, M.-A., and Barragan, Antonio
- Abstract
Upon pathogen detection, macrophages normally stay sessile in tissues while dendritic cells (DCs) migrate to secondary lymphoid tissues. The obligate intracellular protozoan Toxoplasma gondii exploits the trafficking of mononuclear phagocytes for dissemination via unclear mechanisms. We report that, upon T. gondii infection, macrophages initiate the expression of transcription factors normally attributed to DCs, upregulate CCR7 expression with a chemotactic response, and perform systemic migration when adoptively transferred into mice. We show that parasite effector GRA28, released by the MYR1 secretory pathway, cooperates with host chromatin remodelers in the host cell nucleus to drive the chemotactic migration of parasitized macrophages. During in vivo challenge studies, bone marrow-derived macrophages infected with wild-type T. gondii outcompeted those challenged with MYR1- or GRA28-deficient strains in migrating and reaching secondary organs. This work reveals how an intracellular parasite hijacks chemotaxis in phagocytes and highlights a remarkable migratory plasticity in differentiated cells of the mononuclear phagocyte system.
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- 2022
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4. SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation-Phosphorylation Cross-talk
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Lukinovic, V., Hausmann, S., Roth, G. S., Oyeniran, C., Ahmad, T., Tsao, N., Brickner, J. R., Casanova, A. G., Chuffart, F., Benitez, A. M., Vayr, J., Rodell, R., Tardif, M., Jansen, P. W., Couté, Y., Vermeulen, M., Hainaut, P., Mazur, P.K., Mosammaparast, N., Reynoird, N., Lukinovic, V., Hausmann, S., Roth, G. S., Oyeniran, C., Ahmad, T., Tsao, N., Brickner, J. R., Casanova, A. G., Chuffart, F., Benitez, A. M., Vayr, J., Rodell, R., Tardif, M., Jansen, P. W., Couté, Y., Vermeulen, M., Hainaut, P., Mazur, P.K., Mosammaparast, N., and Reynoird, N.
- Abstract
Contains fulltext : 283880.pdf (Publisher’s version ) (Open Access)
- Published
- 2022
5. V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors
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Nguyen-Lefebvre, A T, Leprun, G, Morin, V, Viñuelas, J, Couté, Y, Madjar, J-J, Gandrillon, O, and Gonin-Giraud, S
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- 2014
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6. Unbalanced expression of CK2 kinase subunits is sufficient to drive epithelial-to-mesenchymal transition by Snail1 induction
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Deshiere, A, Duchemin-Pelletier, E, Spreux, E, Ciais, D, Combes, F, Vandenbrouck, Y, Couté, Y, Mikaelian, I, Giusiano, S, Charpin, C, Cochet, C, and Filhol, O
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- 2013
- Full Text
- View/download PDF
7. Constrained G4 structures unveil topology specificity of known and new G4 binding proteins
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Pipier, A., primary, Devaux, A., additional, Lavergne, T., additional, Adrait, A., additional, Couté, Y., additional, Britton, S., additional, Calsou, P., additional, Riou, J.F., additional, Defrancq, E., additional, and Gomez, D., additional
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- 2021
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8. The protein ICP0 of herpes simplex virus type 1 is targeted to nucleoli of infected cells
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Morency, E., Couté, Y., Thomas, J., Texier, P., and Lomonte, P.
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- 2005
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9. A peptide-level multiple imputation strategy accounting for the different natures of missing values in proteomics data
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Gianetto, Q. Giai, primary, Wieczorek, S., additional, Couté, Y., additional, and Burger, T., additional
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- 2020
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10. Pre- and Post-analytical Factors in Biomarker Discovery
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Klont, Frank, Horvatovich, Peter, Govorukhina, Natalia, Bischoff, Rainer, Brun, V., Couté, Y., Analytical Biochemistry, and Medicinal Chemistry and Bioanalysis (MCB)
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0301 basic medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Computer science ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Sample preparation ,Computational biology ,Biomarker discovery ,Proteomics ,Mass spectrometry ,Pre and post - Abstract
The translation of promising biomarkers, which were identified in biomarker discovery experiments, to clinical assays is one of the key challenges in present-day proteomics research. Many so-called "biomarker candidates" fail to progress beyond the discovery phase, and much emphasis is placed on pre- and post-analytical variability in an attempt to provide explanations for this bottleneck in the biomarker development pipeline. With respect to such variability, there is a large number of pre- and post-analytical factors which may impact the outcomes of proteomics experiments and thus necessitate tight control. This chapter highlights some of these factors and provides guidance for addressing them on the basis of examples from previously published proteomics studies.
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- 2019
11. Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells
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Shiota, H, Barral, S, Buchou, T, Tan, M, Couté, Y, Charbonnier, G, Reynoird, N, Boussouar, F, Gérard, M, Zhu, M, Bargier, L, Puthier, D, Chuffart, F, Bourova-Flin, E, Picaud, S, Filippakopoulos, P, Goudarzi, A, Ibrahim, Z, Panne, D, Rousseaux, S, Zhao, Y, Khochbin, S, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Shanghai Institute of Materia Medica, Chinese Academy of Sciences [Changchun Branch] (CAS), Etude de la dynamique des protéomes (EDyP ), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche du CEA/DSV/iBiTec-S/SIMOPRO, Structural Genomics Consortium, University of Oxford, European Molecular Biology Laboratory [Grenoble] (EMBL), Ben May Department of Cancer Research, The University of Chicago Medicine, ANR-15-IDEX-0002,UGA,IDEX UGA(2015), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010), European Project: 289880,EC:FP7:PEOPLE,FP7-PEOPLE-2011-ITN,REPRO-TRAIN(2012), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Etude de la dynamique des protéomes (EDyP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Technologies avancées pour le génôme et la clinique (TAGC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de l'Informatique du Parallélisme (LIP), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford], Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])
- Subjects
Male ,Midline ,Xenopus ,[SDV]Life Sciences [q-bio] ,Carcinoma Cells ,Protamine ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Histones ,Mice ,Animals ,p300-CBP Transcription Factors ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Spermatogenesis ,lcsh:QH301-705.5 ,Infertility, Male ,ComputingMilieux_MISCELLANEOUS ,Nut ,Genome ,digestive, oral, and skin physiology ,Nuclear Proteins ,food and beverages ,Acetylation ,Spermatozoa ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,Neoplasm Proteins ,Histone Code ,lcsh:Biology (General) ,Protein Processing, Post-Translational ,Protein Binding - Abstract
International audience; Graphical Abstract Highlights d Nut is a post-meiotically expressed gene that is critical for male fertility d Nut recruits p300 and/or CBP to enhance histone H4K5 and H4K8 acetylation d Nut-mediated histone hyperacetylation is required for histone-to-protamine transition A transcription-independent histone hyperacetylation is associated with near-total histone replacement during mouse spermatogenesis. Shiota et al. show the oncogenic factor Nut is expressed in post-meiotic male germ cells, where it recruits p300 and/or CBP and enhances histone H4K5 and H4K8 acetylation, leading to histone-to-protamine replacement.Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyper-acetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, theinactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome.
- Published
- 2018
12. Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3 HDAC complex
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Beurton, F., primary, Stempor, P., additional, Caron, M., additional, Appert, A., additional, Dong, Y., additional, Chen, R., additional, Cluet, D., additional, Couté, Y., additional, Herbette, M., additional, Huang, N., additional, Polveche, H., additional, Spichty, M., additional, Bedet, C., additional, Ahringer, J., additional, and Palladino, F., additional
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- 2018
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13. PO-151 Variation of ribosome composition and translational reprogramming during human mammary epithelial-to-mesenchymal transition
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Nguyen Van Long, F., primary, Pion, N., additional, Couté, Y., additional, Morel, A.P., additional, Marchand, V., additional, Motorin, Y., additional, Namy, O., additional, Puisieux, A., additional, Diaz, J.J., additional, and Marcel, V., additional
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- 2018
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14. Identification of hepatitis B virus core protein nuclear interacting factors points to RNA binding proteins as major regulators of HBV replication
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Chabrolles, H., primary, Vegna, S., additional, Héloïse, A., additional, Couté, Y., additional, Belmudes, L., additional, Kim, Y., additional, Arnold, L., additional, Grierson, D., additional, Chabot, B., additional, Combet, C., additional, Zoulim, F., additional, Lucifora, J., additional, Durantel, D., additional, and Salvetti, A., additional
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- 2018
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15. DAPAR & ProStaR: Software to perform statistical analyses in quantitative discovery proteomics
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University of Cambridge, Wieczorek, S., Combes, F., Lazar, C., Gianetto, Q.G., Gatto, Laurent, Dorffer, A., Hesse, A.-M., Couté, Y., Ferro, M., Bruley, C., Burger, T., University of Cambridge, Wieczorek, S., Combes, F., Lazar, C., Gianetto, Q.G., Gatto, Laurent, Dorffer, A., Hesse, A.-M., Couté, Y., Ferro, M., Bruley, C., and Burger, T.
- Published
- 2017
16. Regulation of Postsynaptic Function by the Dementia-Related ESCRT-III Subunit CHMP2B
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Chassefeyre, R., Martinez-Hernandez, J., Bertaso, F., Bouquier, N., Blot, B., Laporte, M., Fraboulet, S., Couté, Y., Devoy, A., Isaacs, M., Pernet-Gallay, K., Sadoul, R., Fagni, Laurent, Goldberg, Y., Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, University College of London [London] (UCL), Institut de Génomique Fonctionnelle (IGF), and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)
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[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2015
17. SAT-352 - Identification of hepatitis B virus core protein nuclear interacting factors points to RNA binding proteins as major regulators of HBV replication
- Author
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Chabrolles, H., Vegna, S., Héloïse, A., Couté, Y., Belmudes, L., Kim, Y., Arnold, L., Grierson, D., Chabot, B., Combet, C., Zoulim, F., Lucifora, J., Durantel, D., and Salvetti, A.
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- 2018
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18. V-erbA generates ribosomes devoid of RPL11 and regulates translational activity in avian erythroid progenitors
- Author
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Nguyen-Lefebvre, A T, primary, Leprun, G, additional, Morin, V, additional, Viñuelas, J, additional, Couté, Y, additional, Madjar, J-J, additional, Gandrillon, O, additional, and Gonin-Giraud, S, additional
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- 2013
- Full Text
- View/download PDF
19. Unbalanced expression of CK2 kinase subunits is sufficient to drive epithelial-to-mesenchymal transition by Snail1 induction
- Author
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Deshiere, A, primary, Duchemin-Pelletier, E, additional, Spreux, E, additional, Ciais, D, additional, Combes, F, additional, Vandenbrouck, Y, additional, Couté, Y, additional, Mikaelian, I, additional, Giusiano, S, additional, Charpin, C, additional, Cochet, C, additional, and Filhol, O, additional
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- 2012
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20. Une vue protéomique des tumeurs endocrines
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Diaz, J.-J., primary, Couderc, C., additional, Couté, Y., additional, Poncet, G., additional, Pourpe, S., additional, Hacot, S., additional, Borson-Chazot, F., additional, Aguerra, K., additional, Scoazec, J.-Y., additional, Sanchez, J.-C., additional, and Roche, C., additional
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- 2008
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21. Proteomic Analysis of the SH2 Domain-containing Leukocyte Protein of 76 kDa (SLP76) Interactome in Resting and Activated Primary Mast Cells
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Bounab Y, Anne-Marie-Hesse, Iannascoli B, Grieco L, Couté Y, Niarakis A, Roncagalli R, Lie E, Lam K, Demangel C, Denis Thieffry, Garin J, Malissen B, and Daëron M
22. Looking for missing proteins in the proteome of human spermatozoa: an update
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Vandenbrouck Y, Lane L, Carapito C, Duek P, Rondel K, Bruley C, Macron C, Gonzalez de Peredo A, Couté Y, Chaoui K, Com E, Gateau A, Am, Hesse, Marcellin M, Mear L, Mouton-Barbosa E, Robin T, Burlet-Schiltz O, Cianférani S, and Ferro M
23. Stable GDP-tubulin islands rescue dynamic microtubules.
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Bagdadi N, Wu J, Delaroche J, Serre L, Delphin C, De Andrade M, Carcel M, Nawabi H, Pinson B, Vérin C, Couté Y, Gory-Fauré S, Andrieux A, Stoppin-Mellet V, and Arnal I
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- Animals, Guanosine Triphosphate metabolism, Humans, Microtubules metabolism, Tubulin metabolism, Tubulin genetics, Guanosine Diphosphate metabolism
- Abstract
Microtubules are dynamic polymers that interconvert between phases of growth and shrinkage, yet they provide structural stability to cells. Growth involves hydrolysis of GTP-tubulin to GDP-tubulin, which releases energy that is stored within the microtubule lattice and destabilizes it; a GTP cap at microtubule ends is thought to prevent GDP subunits from rapidly dissociating and causing catastrophe. Here, using in vitro reconstitution assays, we show that GDP-tubulin, usually considered inactive, can itself assemble into microtubules, preferentially at the minus end, and promote persistent growth. GDP-tubulin-assembled microtubules are highly stable, displaying no detectable spontaneous shrinkage. Strikingly, islands of GDP-tubulin within dynamic microtubules stop shrinkage events and promote rescues. Microtubules thus possess an intrinsic capacity for stability, independent of accessory proteins. This finding provides novel mechanisms to explain microtubule dynamics., (© 2024 Bagdadi et al.)
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- 2024
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24. Comparative transcriptomics reveal a novel tardigrade-specific DNA-binding protein induced in response to ionizing radiation.
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Anoud M, Delagoutte E, Helleu Q, Brion A, Duvernois-Berthet E, As M, Marques X, Lamribet K, Senamaud-Beaufort C, Jourdren L, Adrait A, Heinrich S, Toutirais G, Hamlaoui S, Gropplero G, Giovannini I, Ponger L, Geze M, Blugeon C, Couté Y, Guidetti R, Rebecchi L, Giovannangeli C, De Cian A, and Concordet JP
- Subjects
- Animals, Humans, Gene Expression Profiling, DNA Damage, Radiation Tolerance genetics, Tardigrada genetics, Tardigrada metabolism, Radiation, Ionizing, DNA Repair, DNA-Binding Proteins metabolism, DNA-Binding Proteins genetics, Transcriptome
- Abstract
Tardigrades are microscopic animals renowned for their ability to withstand extreme conditions, including high doses of ionizing radiation (IR). To better understand their radio-resistance, we first characterized induction and repair of DNA double- and single-strand breaks after exposure to IR in the model species Hypsibius exemplaris . Importantly, we found that the rate of single-strand breaks induced was roughly equivalent to that in human cells, suggesting that DNA repair plays a predominant role in tardigrades' radio-resistance. To identify novel tardigrade-specific genes involved, we next conducted a comparative transcriptomics analysis across three different species. In all three species, many DNA repair genes were among the most strongly overexpressed genes alongside a novel tardigrade-specific gene, which we named Tardigrade DNA damage Response 1 ( TDR1 ). We found that TDR1 protein interacts with DNA and forms aggregates at high concentration suggesting it may condensate DNA and preserve chromosome organization until DNA repair is accomplished. Remarkably, when expressed in human cells, TDR1 improved resistance to Bleomycin, a radiomimetic drug. Based on these findings, we propose that TDR1 is a novel tardigrade-specific gene conferring resistance to IR. Our study sheds light on mechanisms of DNA repair helping cope with high levels of DNA damage inflicted by IR., Competing Interests: MA, ED, QH, AB, ED, MA, XM, KL, CS, LJ, AA, SH, GT, SH, GG, IG, LP, MG, CB, YC, RG, LR, CG, AD, JC No competing interests declared, (© 2024, Anoud, Delagoutte, Helleu et al.)
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- 2024
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25. Deciphering the phospho-signature induced by hepatitis B virus in primary human hepatocytes.
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Pastor F, Charles E, Belmudes L, Chabrolles H, Cescato M, Rivoire M, Burger T, Passot G, Durantel D, Lucifora J, Couté Y, and Salvetti A
- Abstract
Phosphorylation is a major post-translation modification (PTM) of proteins which is finely tuned by the activity of several hundred kinases and phosphatases. It controls most if not all cellular pathways including anti-viral responses. Accordingly, viruses often induce important changes in the phosphorylation of host factors that can either promote or counteract viral replication. Among more than 500 kinases constituting the human kinome only few have been described as important for the hepatitis B virus (HBV) infectious cycle, and most of them intervene during early or late infectious steps by phosphorylating the viral Core (HBc) protein. In addition, little is known on the consequences of HBV infection on the activity of cellular kinases. The objective of this study was to investigate the global impact of HBV infection on the cellular phosphorylation landscape early after infection. For this, primary human hepatocytes (PHHs) were challenged or not with HBV, and a mass spectrometry (MS)-based quantitative phosphoproteomic analysis was conducted 2- and 7-days post-infection. The results indicated that while, as expected, HBV infection only minimally modified the cell proteome, significant changes were observed in the phosphorylation state of several host proteins at both time points. Gene enrichment and ontology analyses of up- and down-phosphorylated proteins revealed common and distinct signatures induced by infection. In particular, HBV infection resulted in up-phosphorylation of proteins involved in DNA damage signaling and repair, RNA metabolism, in particular splicing, and cytoplasmic cell-signaling. Down-phosphorylated proteins were mostly involved in cell signaling and communication. Validation studies carried out on selected up-phosphorylated proteins, revealed that HBV infection induced a DNA damage response characterized by the appearance of 53BP1 foci, the inactivation of which by siRNA increased cccDNA levels. In addition, among up-phosphorylated RNA binding proteins (RBPs), SRRM2, a major scaffold of nuclear speckles behaved as an antiviral factor. In accordance with these findings, kinase prediction analysis indicated that HBV infection upregulates the activity of major kinases involved in DNA repair. These results strongly suggest that HBV infection triggers an intrinsic anti-viral response involving DNA repair factors and RBPs that contribute to reduce HBV replication in cell culture models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pastor, Charles, Belmudes, Chabrolles, Cescato, Rivoire, Burger, Passot, Durantel, Lucifora, Couté and Salvetti.)
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- 2024
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26. Plasma ALS and Gal-3BP differentiate early from advanced liver fibrosis in MASLD patients.
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Pérez Compte D, Etourneau L, Hesse AM, Kraut A, Barthelon J, Sturm N, Borges H, Biennier S, Courçon M, de Saint Loup M, Mignot V, Costentin C, Burger T, Couté Y, Bruley C, Decaens T, Jaquinod M, Boursier J, and Brun V
- Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect 30% of the world's population, and its prevalence is increasing in line with obesity. Liver fibrosis is closely related to mortality, making it the most important clinical parameter for MASLD. It is currently assessed by liver biopsy - an invasive procedure that has some limitations. There is thus an urgent need for a reliable non-invasive means to diagnose earlier MASLD stages., Methods: A discovery study was performed on 158 plasma samples from histologically-characterised MASLD patients using mass spectrometry (MS)-based quantitative proteomics. Differentially abundant proteins were selected for verification by ELISA in the same cohort. They were subsequently validated in an independent MASLD cohort (n = 200)., Results: From the 72 proteins differentially abundant between patients with early (F0-2) and advanced fibrosis (F3-4), we selected Insulin-like growth factor-binding protein complex acid labile subunit (ALS) and Galectin-3-binding protein (Gal-3BP) for further study. In our validation cohort, AUROCs with 95% CIs of 0.744 [0.673 - 0.816] and 0.735 [0.661 - 0.81] were obtained for ALS and Gal-3BP, respectively. Combining ALS and Gal-3BP improved the assessment of advanced liver fibrosis, giving an AUROC of 0.796 [0.731. 0.862]. The {ALS; Gal-3BP} model surpassed classic fibrosis panels in predicting advanced liver fibrosis., Conclusions: Further investigations with complementary cohorts will be needed to confirm the usefulness of ALS and Gal-3BP individually and in combination with other biomarkers for diagnosis of liver fibrosis. With the availability of ELISA assays, these findings could be rapidly clinically translated, providing direct benefits for patients., (© 2024. The Author(s).)
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- 2024
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27. Functional redundancy revealed by the deletion of the mimivirus GMC-oxidoreductase genes.
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Alempic JM, Bisio H, Villalta A, Santini S, Lartigue A, Schmitt A, Bugnot C, Notaro A, Belmudes L, Adrait A, Poirot O, Ptchelkine D, De Castro C, Couté Y, and Abergel C
- Abstract
The mimivirus 1.2 Mb genome was shown to be organized into a nucleocapsid-like genomic fiber encased in the nucleoid compartment inside the icosahedral capsid. The genomic fiber protein shell is composed of a mixture of two GMC-oxidoreductase paralogs, one of them being the main component of the glycosylated layer of fibrils at the surface of the virion. In this study, we determined the effect of the deletion of each of the corresponding genes on the genomic fiber and the layer of surface fibrils. First, we deleted the GMC-oxidoreductase, the most abundant in the genomic fiber, and determined its structure and composition in the mutant. As expected, it was composed of the second GMC-oxidoreductase and contained 5- and 6-start helices similar to the wild-type fiber. This result led us to propose a model explaining their coexistence. Then we deleted the GMC-oxidoreductase, the most abundant in the layer of fibrils, to analyze its protein composition in the mutant. Second, we showed that the fitness of single mutants and the double mutant were not decreased compared with the wild-type viruses under laboratory conditions. Third, we determined that deleting the GMC-oxidoreductase genes did not impact the glycosylation or the glycan composition of the layer of surface fibrils, despite modifying their protein composition. Because the glycosylation machinery and glycan composition of members of different clades are different, we expanded the analysis of the protein composition of the layer of fibrils to members of the B and C clades and showed that it was different among the three clades and even among isolates within the same clade. Taken together, the results obtained on two distinct central processes (genome packaging and virion coating) illustrate an unexpected functional redundancy in members of the family Mimiviridae , suggesting this may be the major evolutionary force behind their giant genomes., Competing Interests: The authors declare that they have no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)
- Published
- 2024
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28. Author Correction: Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis.
- Author
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Casanova AG, Roth GS, Hausmann S, Lu X, Bischoff LJM, Froeliger EM, Belmudes L, Bourova-Flin E, Flores NM, Benitez AM, Chasan T, Caporicci M, Vayr J, Blanchet S, Ielasi F, Rousseaux S, Hainaut P, Gozani O, Le Romancer M, Couté Y, Palencia A, Mazur PK, and Reynoird N
- Published
- 2024
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29. Pseudomonas aeruginosa MipA-MipB envelope proteins act as new sensors of polymyxins.
- Author
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Janet-Maitre M, Job V, Bour M, Robert-Genthon M, Brugière S, Triponney P, Cobessi D, Couté Y, Jeannot K, and Attrée I
- Subjects
- Pseudomonas aeruginosa metabolism, Bacterial Proteins metabolism, Anti-Bacterial Agents pharmacology, Bacteria metabolism, Lipopolysaccharides metabolism, Microbial Sensitivity Tests, Polymyxins pharmacology, Polymyxin B pharmacology
- Abstract
Due to the rising incidence of antibiotic-resistant infections, the last-line antibiotics, polymyxins, have resurged in the clinics in parallel with new bacterial strategies of escape. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa develops resistance to colistin/polymyxin B by distinct molecular mechanisms, mostly through modification of the lipid A component of the LPS by proteins encoded within the arnBCDATEF-ugd ( arn ) operon. In this work, we characterized a polymyxin-induced operon named mipBA , present in P. aeruginosa strains devoid of the arn operon. We showed that mipBA is activated by the ParR/ParS two-component regulatory system in response to polymyxins. Structural modeling revealed that MipA folds as an outer-membrane β-barrel, harboring an internal negatively charged channel, able to host a polymyxin molecule, while the lipoprotein MipB adopts a β-lactamase fold with two additional C-terminal domains. Experimental work confirmed that MipA and MipB localize to the bacterial envelope, and they co-purify in vitro . Nano differential scanning fluorimetry showed that polymyxins stabilized MipA in a specific and dose-dependent manner. Mass spectrometry-based quantitative proteomics on P. aeruginosa membranes demonstrated that ∆ mipBA synthesized fourfold less MexXY-OprA proteins in response to polymyxin B compared to the wild-type strain. The decrease was a direct consequence of impaired transcriptional activation of the mex operon operated by ParR/ParS. We propose MipA/MipB to act as membrane (co)sensors working in concert to activate ParS histidine kinase and help the bacterium to cope with polymyxin-mediated envelope stress through synthesis of the efflux pump, MexXY-OprA.IMPORTANCEDue to the emergence of multidrug-resistant isolates, antibiotic options may be limited to polymyxins to eradicate Gram-negative infections. Pseudomonas aeruginosa , a leading opportunistic pathogen, has the ability to develop resistance to these cationic lipopeptides by modifying its lipopolysaccharide through proteins encoded within the arn operon. Herein, we describe a sub-group of P. aeruginosa strains lacking the arn operon yet exhibiting adaptability to polymyxins. Exposition to sub-lethal polymyxin concentrations induced the expression and production of two envelope-associated proteins. Among those, MipA, an outer-membrane barrel, is able to specifically bind polymyxins with an affinity in the 10-µM range. Using membrane proteomics and phenotypic assays, we showed that MipA and MipB participate in the adaptive response to polymyxins via ParR/ParS regulatory signaling. We propose a new model wherein the MipA-MipB module functions as a novel polymyxin sensing mechanism., Competing Interests: The authors declare no conflict of interest.
- Published
- 2024
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30. Large-scale phosphoproteomics reveals activation of the MAPK/GADD45β/P38 axis and cell cycle inhibition in response to BMP9 and BMP10 stimulation in endothelial cells.
- Author
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Al Tarrass M, Belmudes L, Koça D, Azemard V, Liu H, Al Tabosh T, Ciais D, Desroches-Castan A, Battail C, Couté Y, Bouvard C, and Bailly S
- Subjects
- Cell Cycle Checkpoints, Phosphorylation, G1 Phase Cell Cycle Checkpoints, Endothelial Cells, Bone Morphogenetic Proteins
- Abstract
Background: BMP9 and BMP10 are two major regulators of vascular homeostasis. These two ligands bind with high affinity to the endothelial type I kinase receptor ALK1, together with a type II receptor, leading to the direct phosphorylation of the SMAD transcription factors. Apart from this canonical pathway, little is known. Interestingly, mutations in this signaling pathway have been identified in two rare cardiovascular diseases, hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension., Methods: To get an overview of the signaling pathways modulated by BMP9 and BMP10 stimulation in endothelial cells, we employed an unbiased phosphoproteomic-based strategy. Identified phosphosites were validated by western blot analysis and regulated targets by RT-qPCR. Cell cycle analysis was analyzed by flow cytometry., Results: Large-scale phosphoproteomics revealed that BMP9 and BMP10 treatment induced a very similar phosphoproteomic profile. These BMPs activated a non-canonical transcriptional SMAD-dependent MAPK pathway (MEKK4/P38). We were able to validate this signaling pathway and demonstrated that this activation required the expression of the protein GADD45β. In turn, activated P38 phosphorylated the heat shock protein HSP27 and the endocytosis protein Eps15 (EGF receptor pathway substrate), and regulated the expression of specific genes (E-selectin, hyaluronan synthase 2 and cyclooxygenase 2). This study also highlighted the modulation in phosphorylation of proteins involved in transcriptional regulation (phosphorylation of the endothelial transcription factor ERG) and cell cycle inhibition (CDK4/6 pathway). Accordingly, we found that BMP10 induced a G1 cell cycle arrest and inhibited the mRNA expression of E2F2, cyclinD1 and cyclinA1., Conclusions: Overall, our phosphoproteomic screen identified numerous proteins whose phosphorylation state is impacted by BMP9 and BMP10 treatment, paving the way for a better understanding of the molecular mechanisms regulated by BMP signaling in vascular diseases., (© 2024. The Author(s).)
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- 2024
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31. Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis.
- Author
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Casanova AG, Roth GS, Hausmann S, Lu X, Bischoff LJM, Froeliger EM, Belmudes L, Bourova-Flin E, Flores NM, Benitez AM, Chasan T, Caporicci M, Vayr J, Blanchet S, Ielasi F, Rousseaux S, Hainaut P, Gozani O, Le Romancer M, Couté Y, Palencia A, Mazur PK, and Reynoird N
- Abstract
Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cell dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis. While SMYD2 is overexpressed in aggressive breast cancers, we notice that it is not required for primary tumor growth. However, mammary-epithelium specific SMYD2 ablation increases mouse overall survival by blocking the primary tumor cell ability to metastasize. Mechanistically, we identify BCAR3 as a genuine physiological substrate of SMYD2 in breast cancer cells. BCAR3 monomethylated at lysine K334 (K334me1) is recognized by a novel methyl-binding domain present in FMNLs proteins. These actin cytoskeleton regulators are recruited at the cell edges by the SMYD2 methylation signaling and modulate lamellipodia properties. Breast cancer cells with impaired BCAR3 methylation lose migration and invasiveness capacity in vitro and are ineffective in promoting metastases in vivo. Remarkably, SMYD2 pharmacologic inhibition efficiently impairs the metastatic spread of breast cancer cells, PDX and aggressive mammary tumors from genetically engineered mice. This study provides a rationale for innovative therapeutic prevention of malignant breast cancer metastatic progression by targeting the SMYD2-BCAR3-FMNL axis., (© 2024. The Author(s).)
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- 2024
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32. In vitro production of cat-restricted Toxoplasma pre-sexual stages.
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Antunes AV, Shahinas M, Swale C, Farhat DC, Ramakrishnan C, Bruley C, Cannella D, Robert MG, Corrao C, Couté Y, Hehl AB, Bougdour A, Coppens I, and Hakimi MA
- Subjects
- Animals, Humans, Chromatin genetics, Chromatin metabolism, Disease Models, Animal, Epigenesis, Genetic, Merozoites genetics, Nuclear Proteins metabolism, Promoter Regions, Genetic genetics, Protozoan Proteins genetics, Protozoan Proteins metabolism, Toxoplasmosis genetics, Toxoplasmosis parasitology, Toxoplasmosis transmission, Transcription, Genetic, Cats parasitology, In Vitro Techniques methods, Life Cycle Stages genetics, Toxoplasma genetics, Toxoplasma growth & development, Toxoplasma physiology
- Abstract
Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described
1,2 . Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref.1 ), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission., (© 2023. The Author(s).)- Published
- 2024
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33. Arabidopsis eIF4E1 protects the translational machinery during TuMV infection and restricts virus accumulation.
- Author
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Zafirov D, Giovinazzo N, Lecampion C, Field B, Ducassou JN, Couté Y, Browning KS, Robaglia C, and Gallois JL
- Subjects
- Eukaryotic Initiation Factor-4E genetics, Eukaryotic Initiation Factor-4E metabolism, Plants, Genetically Modified metabolism, Plant Diseases genetics, Eukaryotic Initiation Factor-4G metabolism, Arabidopsis metabolism, Potyvirus physiology, Arabidopsis Proteins genetics, Arabidopsis Proteins metabolism
- Abstract
Successful subversion of translation initiation factors eIF4E determines the infection success of potyviruses, the largest group of viruses affecting plants. In the natural variability of many plant species, resistance to potyvirus infection is provided by polymorphisms at eIF4E that renders them inadequate for virus hijacking but still functional in translation initiation. In crops where such natural resistance alleles are limited, the genetic inactivation of eIF4E has been proposed for the engineering of potyvirus resistance. However, recent findings indicate that knockout eIF4E alleles may be deleterious for plant health and could jeopardize resistance efficiency in comparison to functional resistance proteins. Here, we explored the cause of these adverse effects by studying the role of the Arabidopsis eIF4E1, whose inactivation was previously reported as conferring resistance to the potyvirus clover yellow vein virus (ClYVV) while also promoting susceptibility to another potyvirus turnip mosaic virus (TuMV). We report that eIF4E1 is required to maintain global plant translation and to restrict TuMV accumulation during infection, and its absence is associated with a favoured virus multiplication over host translation. Furthermore, our findings show that, in the absence of eIF4E1, infection with TuMV results in the production of a truncated eIFiso4G1 protein. Finally, we demonstrate a role for eIFiso4G1 in TuMV accumulation and in supporting plant fitness during infection. These findings suggest that eIF4E1 counteracts the hijacking of the plant translational apparatus during TuMV infection and underscore the importance of preserving the functionality of translation initiation factors eIF4E when implementing potyvirus resistance strategies., Competing Interests: none., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
- Published
- 2023
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34. SIN-3 acts in distinct complexes to regulate the germline transcriptional program in Caenorhabditis elegans.
- Author
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Robert VJ, Caron M, Gely L, Adrait A, Pakulska V, Couté Y, Chevalier M, Riedel CG, Bedet C, and Palladino F
- Subjects
- Animals, Germ Cells metabolism, Histones metabolism, In Situ Hybridization, Fluorescence, X Chromosome metabolism, Caenorhabditis elegans genetics, Caenorhabditis elegans metabolism, Histone Deacetylases genetics, Histone Deacetylases metabolism, Caenorhabditis elegans Proteins genetics, Caenorhabditis elegans Proteins metabolism, Sin3 Histone Deacetylase and Corepressor Complex genetics, Sin3 Histone Deacetylase and Corepressor Complex metabolism
- Abstract
The transcriptional co-regulator SIN3 influences gene expression through multiple interactions that include histone deacetylases. Haploinsufficiency and mutations in SIN3 are the underlying cause of Witteveen-Kolk syndrome and related intellectual disability and autism syndromes, emphasizing its key role in development. However, little is known about the diversity of its interactions and functions in developmental processes. Here, we show that loss of SIN-3, the single SIN3 homolog in Caenorhabditis elegans, results in maternal-effect sterility associated with de-regulation of the germline transcriptome, including de-silencing of X-linked genes. We identify at least two distinct SIN3 complexes containing specific histone deacetylases and show that they differentially contribute to fertility. Single-cell, single-molecule fluorescence in situ hybridization reveals that in sin-3 mutants the X chromosome becomes re-expressed prematurely and in a stochastic manner in individual germ cells, suggesting a role for SIN-3 in its silencing. Furthermore, we identify histone residues whose acetylation increases in the absence of SIN-3. Together, this work provides a powerful framework for the in vivo study of SIN3 and associated proteins., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)
- Published
- 2023
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35. Cell-type-specific control of secondary cell wall formation by Musashi-type translational regulators in Arabidopsis .
- Author
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Kairouani A, Pontier D, Picart C, Mounet F, Martinez Y, Le-Bot L, Fanuel M, Hammann P, Belmudes L, Merret R, Azevedo J, Carpentier MC, Gagliardi D, Couté Y, Sibout R, Bies-Etheve N, and Lagrange T
- Subjects
- Lignin, Protein Processing, Post-Translational, Cell Wall metabolism, Gene Expression Regulation, Plant, Arabidopsis genetics, Arabidopsis metabolism, Arabidopsis Proteins genetics, Arabidopsis Proteins metabolism
- Abstract
Deciphering the mechanism of secondary cell wall/SCW formation in plants is key to understanding their development and the molecular basis of biomass recalcitrance. Although transcriptional regulation is essential for SCW formation, little is known about the implication of post-transcriptional mechanisms in this process. Here we report that two bonafide RNA-binding proteins homologous to the animal translational regulator Musashi, MSIL2 and MSIL4, function redundantly to control SCW formation in Arabidopsis . MSIL2/4 interactomes are similar and enriched in proteins involved in mRNA binding and translational regulation. MSIL2/4 mutations alter SCW formation in the fibers, leading to a reduction in lignin deposition, and an increase of 4- O -glucuronoxylan methylation. In accordance, quantitative proteomics of stems reveal an overaccumulation of glucuronoxylan biosynthetic machinery, including GXM3, in the msil2/4 mutant stem. We showed that MSIL4 immunoprecipitates GXM mRNAs, suggesting a novel aspect of SCW regulation, linking post-transcriptional control to the regulation of SCW biosynthesis genes., Competing Interests: AK, DP, CP, FM, YM, LL, MF, PH, LB, RM, JA, MC, DG, YC, RS, NB, TL No competing interests declared, (© 2023, Kairouani, Pontier et al.)
- Published
- 2023
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36. A Proteomics-Based Approach Identifies the NEDD4 Adaptor NDFIP2 as an Important Regulator of Ifitm3 Levels.
- Author
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Marziali F, Song Y, Nguyen XN, Belmudes L, Burlaud-Gaillard J, Roingeard P, Couté Y, and Cimarelli A
- Subjects
- Protein Processing, Post-Translational, Lysosomes metabolism, Antiviral Agents metabolism, Proteomics, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism
- Abstract
IFITMs are a family of highly related interferon-induced transmembrane proteins that interfere with the processes of fusion between viral and cellular membranes and are thus endowed with broad antiviral properties. A number of studies have shown how the antiviral potency of IFITMs is highly dependent on their steady-state levels, their intracellular distribution and a complex pattern of post-translational modifications, parameters that are overall tributary of a number of cellular partners. In an effort to identify additional protein partners involved in the biology of IFITMs, we devised a proteomics-based approach based on the piggyback incorporation of IFITM3 partners into extracellular vesicles. MS analysis of the proteome of vesicles bearing or not bearing IFITM3 identified the NDFIP2 protein adaptor protein as an important regulator of IFITM3 levels. NDFIP2 is a membrane-anchored adaptor protein of the E3 ubiquitin ligases of the NEDD4 family that have already been found to be involved in IFITM3 regulation. We show here that NDFIP2 acts as a recruitment factor for both IFITM3 and NEDD4 and mediates their distribution in lysosomal vesicles. The genetic inactivation and overexpression of NDFIP2 drive, respectively, lower and higher levels of IFITM3 accumulation in the cell, overall suggesting that NDFIP2 locally competes with IFITM3 for NEDD4 binding. Given that NDFIP2 is itself tightly regulated and highly responsive to external cues, our study sheds light on a novel and likely dynamic layer of regulation of IFITM3.
- Published
- 2023
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37. Cytoskeleton remodeling induced by SMYD2 methyltransferase drives breast cancer metastasis.
- Author
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Casanova AG, Roth GS, Hausmann S, Lu X, Belmudes L, Bourova-Flin E, Flores NM, Benitez AM, Caporicci M, Vayr J, Blanchet S, Ielasi F, Rousseaux S, Hainaut P, Gozani O, Couté Y, Palencia A, Mazur PK, and Reynoird N
- Abstract
Malignant forms of breast cancer refractory to existing therapies remain a major unmet health issue, primarily due to metastatic spread. A better understanding of the mechanisms at play will provide better insights for alternative treatments to prevent breast cancer cells dispersion. Here, we identify the lysine methyltransferase SMYD2 as a clinically actionable master regulator of breast cancer metastasis. While SMYD2 is overexpressed in aggressive breast cancers, we notice that it is not required for primary tumor growth. However, mammary-epithelium specific SMYD2 ablation increases mouse overall survival by blocking the primary tumor cells ability to metastasize. Mechanistically, we identify BCAR3 as a genuine physiological substrate of SMYD2 in breast cancer cells. BCAR3 monomethylated at lysine K334 (K334me1) is recognized by a novel methyl-binding domain present in FMNLs proteins. These actin cytoskeleton regulators are recruited at the cell edges by the SMYD2 methylation signaling and modulates lamellipodia properties. Breast cancer cells with impaired BCAR3 methylation loose migration and invasiveness capacity in vitro and are ineffective in promoting metastases in vivo . Remarkably, SMYD2 pharmacologic inhibition efficiently impairs the metastatic spread of breast cancer cells, PDX and aggressive mammary tumors from genetically engineered mice. This study provides a rationale for innovative therapeutic prevention of malignant breast cancer metastatic progression by targeting the SMYD2-BCAR3-FMNL axis.
- Published
- 2023
- Full Text
- View/download PDF
38. Nucleoside diphosphate kinases 1 and 2 regulate a protective liver response to a high-fat diet.
- Author
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Iuso D, Garcia-Saez I, Couté Y, Yamaryo-Botté Y, Boeri Erba E, Adrait A, Zeaiter N, Tokarska-Schlattner M, Jilkova ZM, Boussouar F, Barral S, Signor L, Couturier K, Hajmirza A, Chuffart F, Bourova-Flin E, Vitte AL, Bargier L, Puthier D, Decaens T, Rousseaux S, Botté C, Schlattner U, Petosa C, and Khochbin S
- Subjects
- Animals, Mice, Diet, High-Fat adverse effects, Epigenesis, Genetic, Histones, Liver, Fatty Acids, Mice, Knockout, Nucleoside-Diphosphate Kinase genetics
- Abstract
The synthesis of fatty acids from acetyl-coenzyme A (AcCoA) is deregulated in diverse pathologies, including cancer. Here, we report that fatty acid accumulation is negatively regulated by nucleoside diphosphate kinases 1 and 2 (NME1/2), housekeeping enzymes involved in nucleotide homeostasis that were recently found to bind CoA. We show that NME1 additionally binds AcCoA and that ligand recognition involves a unique binding mode dependent on the CoA/AcCoA 3' phosphate. We report that Nme2 knockout mice fed a high-fat diet (HFD) exhibit excessive triglyceride synthesis and liver steatosis. In liver cells, NME2 mediates a gene transcriptional response to HFD leading to the repression of fatty acid accumulation and activation of a protective gene expression program via targeted histone acetylation. Our findings implicate NME1/2 in the epigenetic regulation of a protective liver response to HFD and suggest a potential role in controlling AcCoA usage between the competing paths of histone acetylation and fatty acid synthesis.
- Published
- 2023
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39. Fetal Muse-based therapy prevents lethal radio-induced gastrointestinal syndrome by intestinal regeneration.
- Author
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Dushime H, Moreno SG, Linard C, Adrait A, Couté Y, Peltzer J, Messiaen S, Torres C, Bensemmane L, Lewandowski D, Romeo PH, Petit V, and Gault N
- Subjects
- Adult, Mice, Humans, Animals, Cell Differentiation physiology, Interleukin-6 metabolism, Intestines, Alprostadil metabolism, Mesenchymal Stem Cells metabolism
- Abstract
Background: Human multilineage-differentiating stress enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be easily obtained from various adult or fetal tissues. Regenerative effects of Muse cells have been shown in some disease models. Muse cells specifically home in damaged tissues where they exert pleiotropic effects. Exposition of the small intestine to high doses of irradiation (IR) delivered after radiotherapy or nuclear accident results in a lethal gastrointestinal syndrome (GIS) characterized by acute loss of intestinal stem cells, impaired epithelial regeneration and subsequent loss of the mucosal barrier resulting in sepsis and death. To date, there is no effective medical treatment for GIS. Here, we investigate whether Muse cells can prevent lethal GIS and study how they act on intestinal stem cell microenvironment to promote intestinal regeneration., Methods: Human Muse cells from Wharton's jelly matrix of umbilical cord (WJ-Muse) were sorted by flow cytometry using the SSEA-3 marker, characterized and compared to bone-marrow derived Muse cells (BM-Muse). Under gas anesthesia, GIS mice were treated or not through an intravenous retro-orbital injection of 50,000 WJ-Muse, freshly isolated or cryopreserved, shortly after an 18 Gy-abdominal IR. No immunosuppressant was delivered to the mice. Mice were euthanized either 24 h post-IR to assess early small intestine tissue response, or 7 days post-IR to assess any regenerative response. Mouse survival, histological stainings, apoptosis and cell proliferation were studied and measurement of cytokines, recruitment of immune cells and barrier functional assay were performed., Results: Injection of WJ-Muse shortly after abdominal IR highly improved mouse survival as a result of a rapid regeneration of intestinal epithelium with the rescue of the impaired epithelial barrier. In small intestine of Muse-treated mice, an early enhanced secretion of IL-6 and MCP-1 cytokines was observed associated with (1) recruitment of monocytes/M2-like macrophages and (2) proliferation of Paneth cells through activation of the IL-6/Stat3 pathway., Conclusion: Our findings indicate that a single injection of a small quantity of WJ-Muse may be a new and easy therapeutic strategy for treating lethal GIS., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
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40. Inflammasome-independent NLRP3 function enforces ATM activity in response to genotoxic stress.
- Author
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Bodnar-Wachtel M, Huber AL, Gorry J, Hacot S, Burlet D, Gérossier L, Guey B, Goutagny N, Bartosch B, Ballot E, Lecuelle J, Truntzer C, Ghiringhelli F, Py BF, Couté Y, Ballesta A, Lantuejoul S, Hall J, Tissier A, and Petrilli V
- Subjects
- Humans, Immunity, Innate, DNA Damage, Apoptosis genetics, Ataxia Telangiectasia Mutated Proteins genetics, Ataxia Telangiectasia Mutated Proteins metabolism, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein genetics, NLR Family, Pyrin Domain-Containing 3 Protein metabolism
- Abstract
NLRP3 is a pattern recognition receptor with a well-documented role in inducing inflammasome assembly in response to cellular stress. Deregulation of its activity leads to many inflammatory disorders including gouty arthritis, Alzheimer disease, and cancer. Whereas its role in the context of cancer has been mostly explored in the immune compartment, whether NLRP3 exerts functions unrelated to immunity in cancer development remains unexplored. Here, we demonstrate that NLRP3 interacts with the ATM kinase to control the activation of the DNA damage response, independently of its inflammasome activity. NLRP3 down-regulation in both broncho- and mammary human epithelial cells significantly impairs ATM pathway activation, leading to lower p53 activation, and provides cells with the ability to resist apoptosis induced by acute genotoxic stress. Interestingly, NLRP3 expression is down-regulated in non-small cell lung cancers and breast cancers, and its expression positively correlates with patient overall survival. Our findings identify a novel non-immune function for NLRP3 in maintaining genome integrity and strengthen the concept of a functional link between innate immunity and DNA damage sensing pathways to maintain cell integrity., (© 2023 Bodnar-Wachtel et al.)
- Published
- 2023
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41. RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells.
- Author
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Durand S, Bruelle M, Bourdelais F, Bennychen B, Blin-Gonthier J, Isaac C, Huyghe A, Martel S, Seyve A, Vanbelle C, Adrait A, Couté Y, Meyronet D, Catez F, Diaz JJ, Lavial F, Ricci EP, Ducray F, and Gabut M
- Subjects
- Humans, Animals, Mice, Cell Differentiation genetics, Polycomb Repressive Complex 2 metabolism, Embryonic Stem Cells metabolism, Pluripotent Stem Cells
- Abstract
Embryonic stem cell (ESC) fate decisions are regulated by a complex circuitry that coordinates gene expression at multiple levels from chromatin to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key pathways that efficiently control stem cell homeostasis, yet the underlying molecular mechanisms remain largely unknown. Here, we identified RSL24D1 as highly expressed in both mouse and human pluripotent stem cells. RSL24D1 is associated with nuclear pre-ribosomes and is required for the biogenesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors and of components from the Polycomb Repressive Complex 2 (PRC2). While having a moderate impact on differentiation, RSL24D1 depletion significantly alters ESC self-renewal and lineage commitment choices. Altogether, these results demonstrate that RSL24D1-dependant ribosome biogenesis is both required to sustain the expression of pluripotent transcriptional programs and to silence PRC2-regulated developmental programs, which concertedly dictate ESC homeostasis., (© 2023. The Author(s).)
- Published
- 2023
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42. Membrane vesicles released by Lacticaseibacillus casei BL23 inhibit the biofilm formation of Salmonella Enteritidis.
- Author
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da Silva Barreira D, Laurent J, Lourenço J, Novion Ducassou J, Couté Y, Guzzo J, and Rieu A
- Subjects
- Lacticaseibacillus, Biofilms, Salmonella enteritidis, Lacticaseibacillus casei
- Abstract
Biofilms represent a major concern in the food industry and healthcare. The use of probiotic bacteria and their derivatives as an alternative to conventional treatments to fight biofilm development is a promising option that has provided convincing results in the last decades. Recently, membrane vesicles (MVs) produced by probiotics have generated considerable interest due to the diversity of roles they have been associated with. However, the antimicrobial activity of probiotic MVs remains to be studied. In this work, we showed that membrane vesicles produced by Lacticaseibacillus casei BL23 (LC-MVs) exhibited strong antibiofilm activity against Salmonella enterica serovar Enteritidis (S. Enteritidis) without affecting bacterial growth. Furthermore, we found that LC-MVs affected the early stages of S. Enteritidis biofilm development and prevented attachment of bacteria to polystyrene surfaces. Importantly, LC-MVs did not impact the biomass of already established biofilms. We also demonstrated that the antibiofilm activity depended on the proteins associated with the LC-MV fraction. Finally, two peptidoglycan hydrolases (PGHs) were found to be associated with the antibiofilm activity of LC-MVs. Overall, this work allowed to identify the antibiofilm properties of LC-MVs and paved the way for the use of probiotic MVs against the development of negative biofilms., (© 2023. The Author(s).)
- Published
- 2023
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43. Statistical Analysis of Quantitative Peptidomics and Peptide-Level Proteomics Data with Prostar.
- Author
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Tardif M, Fremy E, Hesse AM, Burger T, Couté Y, and Wieczorek S
- Subjects
- Mass Spectrometry methods, Peptides analysis, Software, Proteomics methods, Proteome analysis
- Abstract
Prostar is a software tool dedicated to the processing of quantitative data resulting from mass spectrometry-based label-free proteomics. Practically, once biological samples have been analyzed by bottom-up proteomics, the raw mass spectrometer outputs are processed by bioinformatics tools, so as to identify peptides and quantify them, notably by means of precursor ion chromatogram integration. From that point, the classical workflows aggregate these pieces of peptide-level information to infer protein-level identities and amounts. Finally, protein abundances can be statistically analyzed to find out proteins that are significantly differentially abundant between compared conditions. Prostar original workflow has been developed based on this strategy. However, recent works have demonstrated that processing peptide-level information is often more accurate when searching for differentially abundant proteins, as the aggregation step tends to hide some of the data variabilities and biases. As a result, Prostar has been extended by workflows that manage peptide-level data, and this protocol details their use. The first one, deemed "peptidomics," implies that the differential analysis is conducted at peptide level, independently of the peptide-to-protein relationship. The second workflow proposes to aggregate the peptide abundances after their preprocessing (i.e., after filtering, normalization, and imputation), so as to minimize the amount of protein-level preprocessing prior to differential analysis., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2023
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44. Validation of MS/MS Identifications and Label-Free Quantification Using Proline.
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Dupierris V, Hesse AM, Menetrey JP, Bouyssié D, Burger T, Couté Y, and Bruley C
- Subjects
- Proteomics methods, Software, Proteins chemistry, Databases, Protein, Tandem Mass Spectrometry methods, Proline
- Abstract
In the proteomics field, the production and publication of reliable mass spectrometry (MS)-based label-free quantitative results is a major concern. Due to the intrinsic complexity of bottom-up proteomics experiments (requiring aggregation of data relating to both precursor and fragment peptide ions into protein information, and matching this data across samples), inaccuracies and errors can occur throughout the data-processing pipeline. In a classical label-free quantification workflow, the validation of identification results is critical since errors made at this first stage of the workflow may have an impact on the following steps and therefore on the final result. Although false discovery rate (FDR) of the identification is usually controlled by using the popular target-decoy method, it has been demonstrated that this method can sometimes lead to inaccurate FDR estimates. This protocol shows how Proline can be used to validate identification results by using the method based on the Benjamini-Hochberg procedure and then quantify the identified ions and proteins in a single software environment providing data curation capabilities and computational efficiency., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
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- View/download PDF
45. Immune-Mediated Rippling Muscle Disease Associated With Thymoma and Anti-MURC/Cavin-4 Autoantibodies.
- Author
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Svahn J, Coudert L, Streichenberger N, Kraut A, Gravier-Dumonceau-Mazelier A, Rotard L, Calemard-Michel L, Menassa R, Errazuriz-Cerda E, Chalabreysse L, Osseni A, Vial C, Jomir L, Tronc F, Le Duy D, Bernard E, Gache V, Couté Y, Jacquemond V, Schaeffer L, and Leblanc P
- Subjects
- Humans, Autoantibodies, Proteomics, Thymoma complications, Myasthenia Gravis complications, Myasthenia Gravis diagnosis, Thymus Neoplasms complications, Thymus Neoplasms diagnosis
- Abstract
Objectives: Rippling muscle disease (RMD) is characterized by muscle stiffness, muscle hypertrophy, and rippling muscle induced by stretching or percussion. Hereditary RMD is due to sequence variants in the CAV3 and PTRF/CAVIN1 genes encoding Caveolin-3 or Cavin-1, respectively; a few series of patients with acquired autoimmune forms of RMD (iRMD) associated with AChR antibody-positive myasthenia gravis and/or thymoma have also been described. Recently, MURC/caveolae-associated protein 4 (Cavin-4) autoantibody was identified in 8 of 10 patients without thymoma, highlighting its potential both as a biomarker and as a triggering agent of this pathology. Here, we report the case of a patient with iRMD-AchR antibody negative associated with thymoma., Methods: We suspected a paraneoplastic origin and investigated the presence of specific autoantibodies targeting muscle antigens through a combination of Western blotting and affinity purification coupled with mass spectrometry-based proteomic approaches., Results: We identified circulating MURC/Cavin-4 autoantibodies and found strong similarities between histologic features of the patient's muscle and those commonly reported in caveolinopathies. Strikingly, MURC/Cavin-4 autoantibody titer strongly decreased after tumor resection and immunotherapy correlating with complete disappearance of the rippling phenotype and full patient remission., Discussion: MURC/Cavin-4 autoantibodies may play a pathogenic role in paraneoplastic iRMD associated with thymoma., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
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- 2022
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46. Chromatin-associated YTHDC1 coordinates heat-induced reprogramming of gene expression.
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Timcheva K, Dufour S, Touat-Todeschini L, Burnard C, Carpentier MC, Chuffart F, Merret R, Helsmoortel M, Ferré S, Grézy A, Couté Y, Rousseaux S, Khochbin S, Vourc'h C, Bousquet-Antonelli C, Kiernan R, Seigneurin-Berny D, and Verdel A
- Subjects
- Humans, Heat-Shock Proteins metabolism, Gene Expression, RNA Splicing Factors metabolism, Nerve Tissue Proteins metabolism, Chromatin, Heat-Shock Response genetics
- Abstract
Heat stress (HS) induces a cellular response leading to profound changes in gene expression. Here, we show that human YTHDC1, a reader of N
6 -methyladenosine (m6 A) RNA modification, mostly associates to the chromatin fraction and that HS induces a redistribution of YTHDC1 across the genome, including to heat-induced heat shock protein (HSP) genes. YTHDC1 binding to m6 A-modified HSP transcripts co-transcriptionally promotes expression of HSPs. In parallel, hundreds of the genes enriched in YTHDC1 during HS have their transcripts undergoing YTHDC1- and m6 A-dependent intron retention. Later, YTHDC1 concentrates within nuclear stress bodies (nSBs) where it binds to m6 A-modified SATIII non-coding RNAs, produced in an HSF1-dependent manner upon HS. These findings reveal that YTHDC1 plays a central role in a chromatin-associated m6 A-based reprogramming of gene expression during HS. Furthermore, they support the model where the subsequent and temporary sequestration of YTHDC1 within nSBs calibrates the timing of this YTHDC1-dependent gene expression reprogramming., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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47. Human histone pre-mRNA assembles histone or canonical mRNA-processing complexes by overlapping 3'-end sequence elements.
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Ielasi FS, Ternifi S, Fontaine E, Iuso D, Couté Y, and Palencia A
- Subjects
- Humans, Polyadenylation, mRNA Cleavage and Polyadenylation Factors genetics, RNA, Messenger genetics, RNA, Messenger metabolism, RNA Precursors genetics, RNA Precursors metabolism, Histones genetics, Histones metabolism
- Abstract
Human pre-mRNA processing relies on multi-subunit macromolecular complexes, which recognize specific RNA sequence elements essential for assembly and activity. Canonical pre-mRNA processing proceeds via the recognition of a polyadenylation signal (PAS) and a downstream sequence element (DSE), and produces polyadenylated mature mRNAs, while replication-dependent (RD) histone pre-mRNA processing requires association with a stem-loop (SL) motif and a histone downstream element (HDE), and produces cleaved but non-polyadenylated mature mRNAs. H2AC18 mRNA, a specific H2A RD histone pre-mRNA, can be processed to give either a non-polyadenylated mRNA, ending at the histone SL, or a polyadenylated mRNA. Here, we reveal how H2AC18 captures the two human pre-mRNA processing complexes in a mutually exclusive mode by overlapping a canonical PAS (AAUAAA) sequence element with a HDE. Disruption of the PAS sequence on H2AC18 pre-mRNA prevents recruitment of the canonical complex in vitro, without affecting the histone machinery. This shows how the relative position of cis-acting elements in histone pre-mRNAs allows the selective recruitment of distinct human pre-mRNA complexes, thereby expanding the capability to regulate 3' processing and polyadenylation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2022
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48. Structure of the human heparan sulfate polymerase complex EXT1-EXT2.
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Leisico F, Omeiri J, Le Narvor C, Beaudouin J, Hons M, Fenel D, Schoehn G, Couté Y, Bonnaffé D, Sadir R, Lortat-Jacob H, and Wild R
- Subjects
- Humans, Cryoelectron Microscopy, Proteins metabolism, Nucleotidyltransferases, Glycosyltransferases metabolism, N-Acetylglucosaminyltransferases metabolism, Heparitin Sulfate metabolism
- Abstract
Heparan sulfates are complex polysaccharides that mediate the interaction with a broad range of protein ligands at the cell surface. A key step in heparan sulfate biosynthesis is catalyzed by the bi-functional glycosyltransferases EXT1 and EXT2, which generate the glycan backbone consisting of repeating N-acetylglucosamine and glucuronic acid units. The molecular mechanism of heparan sulfate chain polymerization remains, however, unknown. Here, we present the cryo-electron microscopy structure of human EXT1-EXT2, which reveals the formation of a tightly packed hetero-dimeric complex harboring four glycosyltransferase domains. A combination of in vitro and in cellulo mutational studies is used to dissect the functional role of the four catalytic sites. While EXT1 can catalyze both glycosyltransferase reactions, our results indicate that EXT2 might only have N-acetylglucosamine transferase activity. Our findings provide mechanistic insight into heparan sulfate chain elongation as a nonprocessive process and lay the foundation for future studies on EXT1-EXT2 function in health and disease., (© 2022. The Author(s).)
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- 2022
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49. SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members.
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Binda O, Juillard F, Ducassou JN, Kleijwegt C, Paris G, Didillon A, Baklouti F, Corpet A, Couté Y, Côté J, and Lomonte P
- Subjects
- Humans, Infant, Motor Neurons metabolism, Proteomics, RNA metabolism, Fragile X Mental Retardation Protein genetics, Fragile X Mental Retardation Protein metabolism, Muscular Atrophy, Spinal genetics, Muscular Atrophy, Spinal metabolism, Survival of Motor Neuron 1 Protein genetics
- Abstract
Although recent advances in gene therapy provide hope for spinal muscular atrophy (SMA) patients, the pathology remains the leading genetic cause of infant mortality. SMA is a monogenic pathology that originates from the loss of the SMN1 gene in most cases or mutations in rare cases. Interestingly, several SMN1 mutations occur within the TUDOR methylarginine reader domain of SMN. We hypothesized that in SMN1 mutant cases, SMA may emerge from aberrant protein-protein interactions between SMN and key neuronal factors. Using a BioID proteomic approach, we have identified and validated a number of SMN-interacting proteins, including fragile X mental retardation protein (FMRP) family members (FMR
FM ). Importantly, SMA-linked SMNTUDOR mutant forms (SMNST ) failed to interact with FMRFM In agreement with the recent work, we define biochemically that SMN forms droplets in vitro and these droplets are stabilized by RNA, suggesting that SMN could be involved in the formation of membraneless organelles, such as Cajal nuclear bodies. Finally, we found that SMN and FMRP co-fractionate with polysomes, in an RNA-dependent manner, suggesting a potential role in localized translation in motor neurons., (© 2022 Binda et al.)- Published
- 2022
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50. The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages.
- Author
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Ten Hoeve AL, Braun L, Rodriguez ME, Olivera GC, Bougdour A, Belmudes L, Couté Y, Saeij JPJ, Hakimi MA, and Barragan A
- Subjects
- Mice, Animals, Dendritic Cells physiology, Cell Movement, Macrophages, Toxoplasma physiology, Parasites
- Abstract
Upon pathogen detection, macrophages normally stay sessile in tissues while dendritic cells (DCs) migrate to secondary lymphoid tissues. The obligate intracellular protozoan Toxoplasma gondii exploits the trafficking of mononuclear phagocytes for dissemination via unclear mechanisms. We report that, upon T. gondii infection, macrophages initiate the expression of transcription factors normally attributed to DCs, upregulate CCR7 expression with a chemotactic response, and perform systemic migration when adoptively transferred into mice. We show that parasite effector GRA28, released by the MYR1 secretory pathway, cooperates with host chromatin remodelers in the host cell nucleus to drive the chemotactic migration of parasitized macrophages. During in vivo challenge studies, bone marrow-derived macrophages infected with wild-type T. gondii outcompeted those challenged with MYR1- or GRA28-deficient strains in migrating and reaching secondary organs. This work reveals how an intracellular parasite hijacks chemotaxis in phagocytes and highlights a remarkable migratory plasticity in differentiated cells of the mononuclear phagocyte system., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
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