Search

Your search keyword '"MESH: RNA-Binding Proteins/genetics"' showing total 2 results
Start Over Descriptor "MESH: RNA-Binding Proteins/genetics" Topic [sdv]life sciences [q-bio]
2 results on '"MESH: RNA-Binding Proteins/genetics"'

1. Comparative Loss-of-Function Screens Reveal ABCE1 as an Essential Cellular Host Factor for Efficient Translation of Paramyxoviridae and Pneumoviridae

Author

Kristmundur Sigmundsson, Danielle E. Anderson, So Young Kim, Zhen Zhen Joanna Yeo, Sharon F. Jamison, Kristin Pfeffermann, James L. Pearson, Bevan Sawatsky, Mikhail Kovtun, Lin-Fa Wang, Pierre J. Talbot, Veronika von Messling, Mariano A. Garcia-Blanco, Yvonne Krebs, David L. Corcoran, Linda J. Rennick, W. Paul Duprex, Duke-NUS Medical School [Singapore], Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines (EPI), Duke University [Durham], National Emerging Infectious Diseases Laboratories (NEIDL), Boston University [Boston] (BU), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), The University of Texas Medical Branch (UTMB), This work was supported by grants CIHR MOP-66989 of the Canadian Institutes of Health Research, CFI 9488 Canada Foundation for Innovation, DZIF TTU Emerging Infections SFB1021 of the German Center for Infection Research, and intramural funding of the German Ministry of Health to V.V.M., NMRC/BNIG/2030/2015 (Singapore) to D.E.A., and USA NIH R01-AI089526 and R01-AI101431 to M.A.G.-B. and R01-AI099100 to W.P.D., and We thank members of our laboratories, past and present, for constructive comments throughout this project. We thank the Duke Functional Genomics Shared Resource for work related to the primary siRNA screens. We are grateful to Jaisri Lingappa for sharing the ABCE1 antibody and peptide sequence during our preliminary studies. We thank Ian Mendenhall for his assistance in the construction of the phylogenetic tree and Kevin Wittwer and Oliver Siering for technical assistance. We greatly appreciate the help provided by Robert Tampé, Ralph Wieneke, and Simon Trowitzsch with the phosphorimager and Andrea Maisner and Marc Ringel with the confocal microscope. We thank Stephan Becker for critical comments on the manuscript.

Subjects
MESH: Gene Expression, Paramyxoviridae, ABCE1, respiratory syncytial virus, [SDV]Life Sciences [q-bio], host factor, MESH: Pneumovirus/pathogenicity, RNA-binding protein, Computational biology, Microbiology, 03 medical and health sciences, Virology, MESH: RNA, Small Interfering, MESH: RNA-Binding Proteins/genetics, MESH: ATP-Binding Cassette Transporters/genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Pneumoviridae, RNAi screen, MESH: RNA, Messenger, 030304 developmental biology, Host factor, 0303 health sciences, MESH: Humans, biology, MESH: Paramyxoviridae/pathogenicity, 030302 biochemistry & molecular biology, Translation (biology), Pneumovirus, biology.organism_classification, QR1-502, MESH: Host Microbial Interactions/genetics, 3. Good health, Vesicular transport protein, biology.protein, MESH: A549 Cells, MESH: Computational Biology
Abstract

International audience; Paramyxoviruses and pneumoviruses have similar life cycles and share the respiratory tract as a point of entry. In comparative genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in A549 cells, a human lung adenocarcinoma cell line, we identified vesicular transport, RNA processing pathways, and translation as the top pathways required by all three viruses. As the top hit in the translation pathway, ABCE1, a member of the ATP-binding cassette transporters, was chosen for further study. We found that ABCE1 supports replication of all three viruses, confirming its importance for viruses of both families. More detailed characterization revealed that ABCE1 is specifically required for efficient viral but not general cellular protein synthesis, indicating that paramyxoviral and pneumoviral mRNAs exploit specific translation mechanisms. In addition to providing a novel overview of cellular proteins and pathways that impact these important pathogens, this study highlights the role of ABCE1 as a host factor required for efficient paramyxovirus and pneumovirus translation.IMPORTANCE The Paramyxoviridae and Pneumoviridae families include important human and animal pathogens. To identify common host factors, we performed genome-scale siRNA screens with wild-type-derived measles, mumps, and respiratory syncytial viruses in the same cell line. A comparative bioinformatics analysis yielded different members of the coatomer complex I, translation factors ABCE1 and eIF3A, and several RNA binding proteins as cellular proteins with proviral activity for all three viruses. A more detailed characterization of ABCE1 revealed its essential role for viral protein synthesis. Taken together, these data sets provide new insight into the interactions between paramyxoviruses and pneumoviruses and host cell proteins and constitute a starting point for the development of broadly effective antivirals.

Published
2019
Full Text
View/download PDF

2. Pleiotropic role of the RNA chaperone protein Hfq in the human pathogen Clostridium difficile

Author

Olga Soutourina, Marc Monot, Bruno Dupuy, Isabelle Martin-Verstraete, Laure Saujet, Eliane Hajnsdorf, Pierre Boudry, Joël Caillet, Céline Gracia, Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7), Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Expression Génétique Microbienne (EGM (UMR_8261 / FRE_3630)), Institut de biologie physico-chimique (IBPC (FR_550)), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the Institut Pasteur, the Centre National de la Recherche Scientifique (FRE3630 and previously UPR9073), Université Paris Diderot and Agence Nationale de la Recherche (asSUPYCO, ANR-12-BSV6-0007-03, CloSTARn, ANR-13-JSV3-0005-01) and by the Initiative d'Excellence program from the French State (grant DYNAMO, ANR-11-LABX-0011). P.B. and L.S. have fellowships from the Université Paris Diderot., We thank Evelyne Couture-Tosi for performing electron microscopy analysis and M. Fujita for providing us with polyclonal anti-SigA antibodies. S.O. and I.M.-V. are assistant and full professors at the Université Paris Diderot, respectively., ANR-12-BSV6-0007,asSUPYCO,Régulation de la maturation et de la dégradation de l'ARN par les ARN antisens(2012), ANR-13-JSV3-0005,CloSTARn,Rôle du c-di-GMP dans le contrôle via des ' riboswitch ' et des ARN antisens de processus cellulaires associés au comportement communautaire chez Clostridium difficile, une bactérie opportuniste responsable d'infections nosocomiales(2013), ANR-11-LABX-0011,DYNAMO,Dynamique des membranes transductrices d'énergie : biogénèse et organisation supramoléculaire.(2011), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes, Expression Génétique Microbienne (EGM), Institut de biologie physico-chimique (IBPC), ANR-13-JSV3-0005,CloSTARn,Rôle du c-di-GMP dans le contrôle via des « riboswitch » et des ARN antisens de processus cellulaires associés au comportement communautaire chez Clostridium difficile, une bactérie opportuniste responsable d'infections nosocomiales(2013), ANR-11-LABX-0011/11-LABX-0011,DYNAMO,Dynamique des membranes transductrices d'énergie : biogénèse et organisation supramoléculaire.(2011), and PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7)

Subjects
MESH: Signal Transduction, MESH: Clostridium difficile/metabolism, [SDV]Life Sciences [q-bio], RNA-binding protein, MESH: RNA-Binding Proteins/metabolism, MESH: Spores, Bacterial, Sigma factor, MESH: RNA-Binding Proteins/genetics, Gene expression, MESH: RNA, Antisense, MESH: Stress, Physiological, MESH: Gene Expression Regulation, Bacterial/physiology, Hfq protein, Genetics, Spores, Bacterial, MESH: Gene Expression Regulation, Bacterial, MESH: Signal Transduction/physiology, RNA-Binding Proteins, Genetic Pleiotropy, Articles, MESH: RNA, Bacterial/genetics, Clostridium difficile, RNA, Bacterial, Gene Knockdown Techniques, MESH: Molecular Chaperones, MESH: Molecular Chaperones/genetics, MESH: RNA, Bacterial, Signal Transduction, MESH: Mutation, MESH: Clostridium difficile/genetics, MESH: Genetic Pleiotropy, Biology, Microbiology, Stress, Physiological, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Antisense, Molecular Biology, Gene, MESH: Clostridium difficile, MESH: Humans, Clostridioides difficile, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, MESH: Gene Knockdown Techniques, MESH: RNA-Binding Proteins, Regulon, MESH: RNA, Bacterial/metabolism, Mutation, biology.protein, MESH: Molecular Chaperones/metabolism, Molecular Chaperones
Abstract

Clostridium difficile is an emergent human pathogen and the most common cause of nosocomial diarrhea. Our recent data strongly suggest the importance of RNA-based mechanisms for the control of gene expression in C. difficile . In an effort to understand the function of the RNA chaperone protein Hfq, we constructed and characterized an Hfq-depleted strain in C. difficile . Hfq depletion led to a growth defect, morphological changes, an increased sensitivity to stresses, and a better ability to sporulate and to form biofilms. The transcriptome analysis revealed pleiotropic effects of Hfq depletion on gene expression in C. difficile , including genes encoding proteins involved in sporulation, stress response, metabolic pathways, cell wall-associated proteins, transporters, and transcriptional regulators and genes of unknown function. Remarkably, a great number of genes of the regulon dependent on sporulation-specific sigma factor, SigK, were upregulated in the Hfq-depleted strain. The altered accumulation of several sRNAs and interaction of Hfq with selected sRNAs suggest potential involvement of Hfq in these regulatory RNA functions. Altogether, these results suggest the pleiotropic role of Hfq protein in C. difficile physiology, including processes important for the C. difficile infection cycle, and expand our knowledge of Hfq-dependent regulation in Gram-positive bacteria.

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results