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Your search keyword '"MESH: Ribonuclease III"' showing total 12 results
Start Over Descriptor "MESH: Ribonuclease III" Topic 0303 health sciences
12 results on '"MESH: Ribonuclease III"'

1. C19MC microRNAs are processed from introns of large Pol-II, non-protein-coding transcripts

Author

Jérôme Cavaillé, Marie-Line Bortolin-Cavaillé, Michel J. Weber, Marie Dance, Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Service d'ophtalmologie [Nantes], and Hôtel-Dieu

Subjects
Ribonuclease III, MESH: Introns, Placenta, MicroRNA Gene, Gene Expression, RNA polymerase II, MESH: Base Sequence, 0302 clinical medicine, MESH: Ribonuclease III, Gene expression, MESH: Animals, MESH: Alpha-Amanitin, RNA Processing, Post-Transcriptional, Alpha-Amanitin, Genetics, 0303 health sciences, biology, MESH: Placenta, MESH: Primates, 030220 oncology & carcinogenesis, Female, RNA Polymerase II, MESH: RNA Processing, Post-Transcriptional, Primates, MESH: Cell Line, Tumor, MESH: Gene Expression, Molecular Sequence Data, Alu element, RNA polymerase III, 03 medical and health sciences, Cell Line, Tumor, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, Gene, 030304 developmental biology, MESH: RNA, Messenger, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Intron, RNA, Introns, MESH: RNA Polymerase II, MicroRNAs, biology.protein, MESH: Female, MESH: MicroRNAs
Abstract

International audience; MicroRNAs are tiny RNA molecules that play important regulatory roles in a broad range of developmental, physiological or pathological processes. Despite recent progress in our understanding of miRNA processing and biological functions, little is known about the regulatory mechanisms that control their expression at the transcriptional level. C19MC is the largest human microRNA gene cluster discovered to date. This 100-kb long cluster consists of 46 tandemly repeated, primate-specific pre-miRNA genes that are flanked by Alu elements (Alus) and embedded within a approximately 400- to 700-nt long repeated unit. It has been proposed that C19MC miRNA genes are transcribed by RNA polymerase III (Pol-III) initiating from A and B boxes embedded in upstream Alu repeats. Here, we show that C19MC miRNAs are intron-encoded and processed by the DGCR8-Drosha (Microprocessor) complex from a previously unidentified, non-protein-coding Pol-II (and not Pol-III) transcript which is mainly, if not exclusively, expressed in the placenta.

Published
2009
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2. RNA stem–loops: To be or not to be cleaved by RNAse III

Author

Daniel Gautheret, Matthieu Legendre, William Ritchie, Institut de génétique et microbiologie [Orsay] (IGM), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ribonuclease III, MESH: RNA Interference, 0206 medical engineering, MESH: RNA Precursors, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 02 engineering and technology, MESH: Base Sequence, 03 medical and health sciences, MESH: Ribonuclease III, MESH: RNA, RNA interference, microRNA, RNA Precursors, Animals, Humans, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Models, Genetic, Molecular Biology, Protein secondary structure, 030304 developmental biology, Comparative genomics, Genetics, 0303 health sciences, MESH: Humans, Base Sequence, Models, Genetic, biology, MESH: Models, Chemical, RNA, Hypothesis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Models, Structural, MicroRNAs, genomic DNA, MESH: Nucleic Acid Conformation, Models, Chemical, Duplex (building), biology.protein, Nucleic Acid Conformation, RNA Interference, MESH: Models, Structural, MESH: MicroRNAs, 020602 bioinformatics
Abstract

Most of the vertebrate genome is transcribed into RNA. Transcribed regions contain hundreds of thousands of potential duplex structures that could serve as substrates for RNAse III enzymes of microRNA (miRNA) maturation pathways. Yet, only a minority of these potential precursors make their way to the cytoplasm to form mature miRNAs. We question here what specific structural features make an RNA stem–loop structure an adequate primary or precursor miRNA. We address this question by comparing known pre-miRNAs to other predicted noncoding transcripts obtained from comparative genomics scans, using the structure comparison program RNAforester. By analyzing a classification tree of 1200 such RNA structures, we observe that pre-miRNAs cluster distinctly from other duplex structures of apparently similar size and free energy. The most distinctive features of nonprecursor duplexes are increased lengths and numbers of bulges and internal loops when compared to real miRNA precursors. Thanks to these characteristics, secondary structure comparison can predict the miRNA precursor status of a candidate stem–loop with a surprising accuracy. Furthermore, predicted noncoding transcripts tend to depart from miRNA precursor characteristics more strongly than randomly occurring duplex structures in genomic DNA. This result suggests that many noncoding RNAs may be under selection to dodge the RNAi pathway.

Published
2007
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3. The RNA-binding region of human TRBP interacts with microRNA precursors through two independent domains

Author

Andrés Palencia, Christine Ebel, Matthieu P. M. H. Benoit, Jérôme Boisbouvier, Julien Pérard, Lionel Imbert, Michael J. Plevin, Institut de biologie structurale (IBS - UMR 5075 ), 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)-Centre National de la Recherche Scientifique (CNRS), European Molecular Biology Laboratory [Heidelberg] (EMBL), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Ribonuclease III, MESH: RNA Precursors, RNA-binding protein, 03 medical and health sciences, MESH: Protein Structure, Tertiary, 0302 clinical medicine, MESH: Ribonuclease III, RNA interference, microRNA, Gene expression, Genetics, RNA Precursors, Gene silencing, Humans, Binding site, 030304 developmental biology, 0303 health sciences, Binding Sites, MESH: Humans, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], RNA, RNA-Binding Proteins, Molecular biology, Cell biology, Protein Structure, Tertiary, MicroRNAs, MESH: RNA-Binding Proteins, MESH: Binding Sites, biology.protein, MESH: MicroRNAs, 030217 neurology & neurosurgery, Dicer
Abstract

International audience; MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through RNA interference. Human miRNAs are generated through a series of enzymatic processing steps. The precursor miRNA (pre-miRNA) is recognized and cleaved by a complex containing Dicer and several non-catalytic accessory proteins. HIV TAR element binding protein (TRBP) is a constituent of the Dicer complex, which augments complex stability and potentially functions in substrate recognition and product transfer to the RNA-induced silencing complex. Here we have analysed the interaction between the RNA-binding region of TRBP and an oncogenic human miRNA, miR-155, at different stages in the biogenesis pathway. We show that the region of TRBP that binds immature miRNAs comprises two independent double-stranded RNA-binding domains connected by a 60-residue flexible linker. No evidence of contact between the two double-stranded RNA-binding domains was observed either in the apo- or RNA-bound state. We establish that the RNA-binding region of TRBP interacts with both pre-miR-155 and the miR-155/miR-155* duplex through the same binding surfaces and with similar affinities, and that two protein molecules can simultaneously interact with each immature miRNA. These data suggest that TRBP could play a role before and after processing of pre-miRNAs by Dicer.

Published
2013
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4. Selective autophagy degrades DICER and AGO2 and regulates miRNA activity

Author

Olivier Voinnet, Pascale Cossart, Derrick Gibbings, Florence Jay, Yannick Schwab, Serge Mostowy, Dept Biol, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Dept Cellular & Mol Med, University of Ottawa [Ottawa], Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imperial College London, Centre National de la Recherche Scientifique (CNRS), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), ETH-Z, Pasteur Institute, USC2020, Inst Natl Rech Agron, Institut Pasteur [Paris], Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), and ProdInra, Migration

Subjects
Ribonuclease III, [SDV]Life Sciences [q-bio], P-BODIES, Cellular homeostasis, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, PATHWAY, 0302 clinical medicine, MESH: Argonaute Proteins, MESH: Ribonuclease III, MESH: Reverse Transcriptase Polymerase Chain Reaction, ARGONAUTE, NDP52, MESH: Microscopy, Confocal, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Microscopy, Confocal, MESSENGER-RNA DECAY, microRNA, biology, Reverse Transcriptase Polymerase Chain Reaction, Effector, Nuclear Proteins, LOCALIZATION, Argonaute, Cell biology, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Argonaute Proteins, COMPLEXES, MESH: Cell Line, Tumor, PROTEINS, MESH: Microscopy, Electron, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, BAG3, Article, Cell Line, 03 medical and health sciences, Cell Line, Tumor, TRANSLATIONAL REPRESSION, Autophagy, Humans, Immunoprecipitation, MESH: Autophagy, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, post-transcriptional, MESH: Humans, MESH: Immunoprecipitation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cell Biology, DICER, MICRORNA BIOGENESIS, MESH: Cell Line, MicroRNAs, Microscopy, Electron, CELLS, MESH: HeLa Cells, biology.protein, MESH: MicroRNAs, MESH: Nuclear Proteins, HeLa Cells, Dicer
Abstract

International audience; MicroRNAs (miRNAs) form a class of short RNAs (similar to 21 nucleotides) that post-transcriptionally regulate partially complementary messenger RNAs. Each miRNA may target tens to hundreds of transcripts to control key biological processes. Although the biochemical reactions underpinning miRNA biogenesis and activity are relatively well defined(1,2) and the importance of their homeostasis is increasingly evident, the processes underlying regulation of the miRNA pathway in vivo are still largely elusive(3). Autophagy, a degradative process in which cytoplasmic material is targeted into double-membrane vacuoles, is recognized to critically contribute to cellular homeostasis. Here, we show that the miRNA-processing enzyme, DICER (also known as DICER 1), and the main miRNA effector, AGO2 (also known as eukaryotic translation initiation factor 2C, 2 (EIF2C2)), are targeted for degradation as miRNA-free entities by the selective autophagy receptor NDP52 (also known as calcium binding and coiled-coil domain 2 (CALCOCO2)). Autophagy establishes a checkpoint required for continued loading of miRNA into AGO2; accordingly, NDP52 and autophagy are required for homeostasis and activity of the tested miRNAs. Autophagy also engages post-transcriptional regulation of the DICER mRNA, underscoring the importance of fine-tuned regulation of the miRNA pathway. These findings have implications for human diseases linked to misregulated autophagy, DICER- and miRNA-levels, including cancer.

Published
2012
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5. Human prion protein binds Argonaute and promotes accumulation of microRNA effector complexes

Author

Thierry Lagrange, Fabrice Michel, Pascal Leblanc, Florence Jay, Sandrine Alais, Olivier Voinnet, Yannick Schwab, Derrick Gibbings, Dominique Pontier, Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Ecoépidémiologie évolutionniste, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup (VAS)-Centre National de la Recherche Scientifique (CNRS), Service Anesthésie et Réanimation [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Oncogenèse rétrovirale – Retroviral Oncogenesis, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Thiriet, Lydie

Subjects
Ribonuclease III, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, animal diseases, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, RNA-binding protein, Plasma protein binding, MESH: Amino Acid Sequence, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Autoantigens, Mice, MESH: Protein Structure, Tertiary, 0302 clinical medicine, MESH: Argonaute Proteins, MESH: Ribonuclease III, Structural Biology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, Peptide sequence, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Effector, RNA-Binding Proteins, Argonaute, Transmembrane protein, Cell biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Autoantigens, Argonaute Proteins, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Protein Binding, Molecular Sequence Data, Context (language use), Biology, Cell Line, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Gene silencing, MESH: Protein Binding, PrPC Proteins, MESH: PrPC Proteins, Amino Acid Sequence, RNA, Messenger, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, MESH: Mice, 030304 developmental biology, MESH: RNA, Messenger, MESH: Humans, MESH: Molecular Sequence Data, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Protein Structure, Tertiary, nervous system diseases, MESH: Cell Line, MicroRNAs, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, MESH: RNA-Binding Proteins, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: MicroRNAs, 030217 neurology & neurosurgery
Abstract

International audience; Despite intense research in the context of neurodegenerative diseases associated with its misfolding, the endogenous human prion protein PrP(C) (or PRNP) has poorly understood physiological functions. Whereas most PrP(C) is exposed to the extracellular environment, conserved domains result in transmembrane forms of PrP(C) that traffic in the endolysosomal system and are linked to inherited and infectious neuropathologies. One transmembrane PrP(C) variant orients the N-terminal 'octarepeat' domain into the cytoplasm. Here we demonstrate that the octarepeat domain of human PrP(C) contains GW/WG motifs that bind Argonaute (AGO) proteins, the essential components of microRNA (miRNA)-induced silencing complexes (miRISCs). Transmembrane PrP(C) preferentially binds AGO, and PrP(C) promotes formation or stability of miRISC effector complexes containing the trinucleotide repeat-containing gene 6 proteins (TNRC6) and miRNA-repressed mRNA. Accordingly, effective repression of several miRNA targets requires PrP(C). We propose that dynamic interactions between PrP(C)-enriched endosomes and subcellular foci of AGO underpin these effects.

Published
2012
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6. Loss of Dicer in Sertoli cells has a major impact on the testicular proteome of mice

Author

Charles E. Vejnar, Marguerite Neerman-Arbez, Charles Pineau, Antoine Rolland, Olivier Schaad, Serge Nef, Marilena D. Papaioannou, Florian Guillou, Alexandre Fort, Mélanie Lagarrigue, Patrick Descombes, Evgeny M. Zdobnov, Florence Aubry, Françoise Kühne, Department of Genetic Medicine and Development [Geneva], Université de Genève (UNIGE), Virus, Environnement et Reproduction, Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)-Swiss Institute of Bioinformatics (SIB), Swiss Institute of Bioinformatics-Swiss Institute of Bioinformatics, Swiss Institute of Bioinformatics (SIB), Swiss Institute of Bioinformatics, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Institut National de la Recherche Agronomique (INRA)-IFR140-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Genomics Platform, University of Geneva [Switzerland]-National Center of Competence in Research ‘Frontiers in Genetics', Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Institut Français du Cheval et de l'Equitation [Saumur]-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Institut National de la Recherche Agronomique (INRA)-Institut National de la Recherche Agronomique (INRA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS), Université de Genève = University of Geneva (UNIGE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Université de Lausanne = University of Lausanne (UNIL), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Station commune de Recherches en Ichtyophysiologie, Biodiversité et Environnement (SCRIBE), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Genève = University of Geneva (UNIGE)-National Center of Competence in Research ‘Frontiers in Genetics', Institut National de la Recherche Agronomique (INRA)-Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Superoxide Dismutase/genetics/metabolism, Enzymologic, Ribonuclease III, Male, Transcription, Genetic, Proteome, Ribonuclease III/deficiency/genetics, Proteome/metabolism, Inbred C57BL, Biochemistry, Transgenic, Analytical Chemistry, Mice, Superoxide Dismutase-1, MESH: Ribonuclease III, Genes, Reporter, Luciferases, Firefly, RNA interference, Tandem Mass Spectrometry, Testis, MESH: Up-Regulation, ddc:576.5, MESH: Animals, Promoter Regions, Genetic, Luciferases, Luciferases, Firefly/biosynthesis/genetics, 3' Untranslated Regions, MESH: Superoxide Dismutase, Sequence Deletion, Regulation of gene expression, 0303 health sciences, MESH: Testis, MESH: Gene Expression Regulation, Enzymologic, Testis/metabolism/pathology, 030302 biochemistry & molecular biology, MESH: 3' Untranslated Regions, MESH: Sequence Deletion, Sertoli cell, Up-Regulation, MESH: Proteome, medicine.anatomical_structure, RNA Interference, Transcription, Germ cell, MESH: Mice, Transgenic, MESH: RNA Interference, Mice, Transgenic, Biology, Gene Expression Regulation, Enzymologic, Promoter Regions, MicroRNAs/genetics/metabolism, 03 medical and health sciences, MESH: Gene Expression Profiling, Genetic, MESH: Sertoli Cells, MESH: Mice, Inbred C57BL, microRNA, MESH: Promoter Regions, Genetic, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Firefly, Reporter, MESH: Mice, 030304 developmental biology, Sertoli Cells, MESH: Luciferases, Firefly, Superoxide Dismutase, Research, Gene Expression Profiling, MESH: Transcription, Genetic, MESH: Genes, Reporter, MESH: Tandem Mass Spectrometry, Molecular biology, MESH: Male, Mice, Inbred C57BL, MicroRNAs, Gene Expression Regulation, Genes, biology.protein, Sertoli Cells/metabolism, Spermatogenesis, MESH: MicroRNAs, Dicer
Abstract

International audience; Sertoli cells (SCs) are the central, essential coordinators of spermatogenesis, without which germ cell development cannot occur. We previously showed that Dicer, an RNaseIII endonuclease required for microRNA (miRNA) biogenesis, is absolutely essential for Sertoli cells to mature, survive, and ultimately sustain germ cell development. Here, using isotope-coded protein labeling, a technique for protein relative quantification by mass spectrometry, we investigated the impact of Sertoli cell-Dicer and subsequent miRNA loss on the testicular proteome. We found that, a large proportion of proteins (50 out of 130) are up-regulated by more that 1.3-fold in testes lacking Sertoli cell-Dicer, yet that this protein up-regulation is mild, never exceeding a 2-fold change, and is not preceeded by alterations of the corresponding mRNAs. Of note, the expression levels of six proteins of interest were further validated using the Absolute Quantification (AQUA) peptide technology. Furthermore, through 3'UTR luciferase assays we identified one up-regulated protein, SOD-1, a Cu/Zn superoxide dismutase whose overexpression has been linked to enhanced cell death through apoptosis, as a likely direct target of three Sertoli cell-expressed miRNAs, miR-125a-3p, miR-872 and miR-24. Altogether, our study, which is one of the few in vivo analyses of miRNA effects on protein output, suggests that, at least in our system, miRNAs play a significant role in translation control.

Published
2011
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7. Recognition of the pre-miRNA structure by Drosophila Dicer-1

Author

Hervé Seitz, Tomoko Kawamata, Natsuko Izumi, Yukihide Tomari, Akihisa Tsutsumi, Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ribonuclease III, Small interfering RNA, MESH: Drosophila Proteins, genetic processes, Substrate Specificity, Terminal loop, MESH: Drosophila melanogaster, 03 medical and health sciences, 0302 clinical medicine, MESH: Ribonuclease III, Structural Biology, microRNA, Animals, Drosophila Proteins, MESH: Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Drosophila, 030304 developmental biology, Genetics, 0303 health sciences, biology, MESH: RNA Helicases, fungi, RNA, Helicase, food and beverages, biology.organism_classification, Cell biology, MicroRNAs, enzymes and coenzymes (carbohydrates), Drosophila melanogaster, biology.protein, MESH: Substrate Specificity, MESH: MicroRNAs, RNA Helicases, 030217 neurology & neurosurgery, Dicer
Abstract

International audience; Drosophila melanogaster has two Dicer proteins with specialized functions. Dicer-1 liberates miRNA-miRNA* duplexes from precursor miRNAs (pre-miRNAs), whereas Dicer-2 processes long double-stranded RNAs into small interfering RNA duplexes. It was recently demonstrated that Dicer-2 is rendered highly specific for long double-stranded RNA substrates by inorganic phosphate and a partner protein R2D2. However, it remains unclear how Dicer-1 exclusively recognize pre-miRNAs. Here we show that fly Dicer-1 recognizes the single-stranded terminal loop structure of pre-miRNAs through its N-terminal helicase domain, checks the loop size and measures the distance between the 3' overhang and the terminal loop. This unique mechanism allows fly Dicer-1 to strictly inspect the authenticity of pre-miRNA structures.

Published
2011
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8. Pom33, a novel transmembrane nucleoporin required for proper nuclear pore complex distribution

Author

Mabel San Roman, Yves Barral, Valérie Doye, Bérangère Lombard, Anne Chadrin, Barbara Hess, Xavier Gatti, Damarys Loew, Benoit Palancade, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institute of Biochemistry, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), and Institut Curie [Paris]

Subjects
Ribonuclease III, Nucleocytoplasmic Transport Proteins, MESH: Sequence Homology, Amino Acid, MESH: Amino Acid Sequence, Endoplasmic Reticulum, 0302 clinical medicine, MESH: Saccharomyces cerevisiae Proteins, MESH: Ribonuclease III, Nuclear pore, MESH: Telophase, MESH: Phylogeny, Integral membrane protein, Research Articles, Phylogeny, 0303 health sciences, MESH: Nucleocytoplasmic Transport Proteins, RNA-Binding Proteins, MESH: Saccharomyces cerevisiae, Transmembrane protein, Cell biology, MESH: Repressor Proteins, Nucleoporin, MESH: Membrane Proteins, MESH: Nuclear Pore, Protein Binding, Saccharomyces cerevisiae Proteins, Recombinant Fusion Proteins, Molecular Sequence Data, Active Transport, Cell Nucleus, Saccharomyces cerevisiae, MESH: Active Transport, Cell Nucleus, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, 03 medical and health sciences, MESH: Endoplasmic Reticulum, MESH: Cell Proliferation, otorhinolaryngologic diseases, MESH: Recombinant Fusion Proteins, MESH: Protein Binding, Amino Acid Sequence, RNA, Messenger, Telophase, Cell Proliferation, 030304 developmental biology, MESH: RNA, Messenger, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, Membrane Proteins, Cell Biology, Nuclear Pore Complex Proteins, Repressor Proteins, stomatognathic diseases, MESH: RNA-Binding Proteins, Membrane protein, Reticulon, Nuclear Pore, 030217 neurology & neurosurgery, Biogenesis, MESH: Nuclear Pore Complex Proteins
Abstract

A previously unrecognized pore membrane protein, Pom33, stabilizes the interface between the nuclear envelope and the NPC to facilitate NPC biogenesis and spatial organization., The biogenesis of nuclear pore complexes (NPCs) represents a paradigm for the assembly of high-complexity macromolecular structures. So far, only three integral pore membrane proteins are known to function redundantly in NPC anchoring within the nuclear envelope. Here, we describe the identification and functional characterization of Pom33, a novel transmembrane protein dynamically associated with budding yeast NPCs. Pom33 becomes critical for yeast viability in the absence of a functional Nup84 complex or Ndc1 interaction network, which are two core NPC subcomplexes, and associates with the reticulon Rtn1. Moreover, POM33 loss of function impairs NPC distribution, a readout for a subset of genes required for pore biogenesis, including members of the Nup84 complex and RTN1. Consistently, we show that Pom33 is required for normal NPC density in the daughter nucleus and for proper NPC biogenesis and/or stability in the absence of Nup170. We hypothesize that, by modifying or stabilizing the nuclear envelope–NPC interface, Pom33 may contribute to proper distribution and/or efficient assembly of nuclear pores.

Published
2010
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9. Argonaute quenching and global changes in Dicer homeostasis caused by a pathogen-encoded GW repeat protein

Author

Laurence Braun, Jacinthe Azevedo, Marc Bergdoll, Olivier Voinnet, Dominique Pontier, Mohamed-Ali Hakimi, Shahinez Garcia, Agnès Yu, Damien Garcia, Thierry Lagrange, Stephanie Ohnesorge, Institut de biologie moléculaire des plantes (IBMP), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Ecoépidémiologie évolutionniste, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Sensorielles Comportement Cognition, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), CNRS UMR 5163 - ATIP+ group, Centre National de la Recherche Scientifique (CNRS), European Organization for Nuclear Research (CERN), Laboratoire Génome et développement des plantes (LGDP), and Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ribonuclease III, 0106 biological sciences, Small interfering RNA, Cell Cycle Proteins, Plasma protein binding, MESH: Amino Acid Sequence, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, 01 natural sciences, MESH: Plant Diseases, MESH: Argonaute Proteins, MESH: Ribonuclease III, RNA interference, Arabidopsis, MESH: RNA, Small Interfering, Homeostasis, MESH: Gene Silencing, RNA, Small Interfering, MESH: Capsid Proteins, ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Effector, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], Argonaute, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Homeostasis, Argonaute Proteins, Host-Pathogen Interactions, Carmovirus, Corrigendum, MESH: Carmovirus, Protein Binding, MESH: Mutation, Molecular Sequence Data, MESH: Sequence Alignment, MESH: Arabidopsis Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, MESH: Cell Cycle Proteins, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Gene silencing, MESH: Protein Binding, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Gene Silencing, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Plant Diseases, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Molecular Sequence Data, Arabidopsis Proteins, fungi, MESH: Host-Pathogen Interactions, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Mutation, biology.protein, Capsid Proteins, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Sequence Alignment, 010606 plant biology & botany, Developmental Biology, Dicer
Abstract

In plants and invertebrates, viral-derived siRNAs processed by the RNaseIII Dicer guide Argonaute (AGO) proteins as part of antiviral RNA-induced silencing complexes (RISC). As a counterdefense, viruses produce suppressor proteins (VSRs) that inhibit the host silencing machinery, but their mechanisms of action and cellular targets remain largely unknown. Here, we show that the Turnip crinckle virus (TCV) capsid, the P38 protein, acts as a homodimer, or multiples thereof, to mimic host-encoded glycine/tryptophane (GW)-containing proteins normally required for RISC assembly/function in diverse organisms. The P38 GW residues bind directly and specifically to Arabidopsis AGO1, which, in addition to its role in endogenous microRNA-mediated silencing, is identified as a major effector of TCV-derived siRNAs. Point mutations in the P38 GW residues are sufficient to abolish TCV virulence, which is restored in Arabidopsis ago1 hypomorphic mutants, uncovering both physical and genetic interactions between the two proteins. We further show how AGO1 quenching by P38 profoundly impacts the cellular availability of the four Arabidopsis Dicers, uncovering an AGO1-dependent, homeostatic network that functionally connects these factors together. The likely widespread occurrence and expected consequences of GW protein mimicry on host silencing pathways are discussed in the context of innate and adaptive immunity in plants and metazoans.

Published
2010
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10. Anopheles gambiae miRNAs as actors of defence reaction against Plasmodium invasion

Author

Sonia Edaye, Flore Winter, Christine Brunel, Alexander Hüttenhofer, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Innsbruck Biocenter, and Innsbrück Biocenter

Subjects
Male, Ribonuclease III, Plasmodium, Anopheles gambiae, MESH: Digestive System, 03 medical and health sciences, MESH: Gene Expression Profiling, 0302 clinical medicine, MESH: Ribonuclease III, Anopheles, parasitic diseases, MESH: Anopheles gambiae, MESH: Gene Library, Genetics, Animals, Gene silencing, Genomic library, MESH: Animals, MESH: Gene Silencing, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene Silencing, Gene Library, 030304 developmental biology, Cloning, 0303 health sciences, biology, MESH: Plasmodium, Gene Expression Profiling, Midgut, biology.organism_classification, MESH: Male, 3. Good health, Gene expression profiling, MicroRNAs, RNA, Female, Digestive System, MESH: Female, MESH: MicroRNAs, 030217 neurology & neurosurgery
Abstract

International audience; The path Plasmodium takes across the Anopheles midgut constitutes the major bottleneck during the malaria transmission cycle. In the present study, using a combination of shot-gun cloning and bioinformatic analysis, we have identified 18 miRNAs from Anopheles gambiae including three miRNAs unique to mosquito. Twelve of them are expressed ubiquitously across the body, independently of gender, while the other six exhibited an expression pattern restricted to the digestive system. Strikingly, the expression patterns of four miRNAs, including the three unique to mosquito, are affected by the presence of Plasmodium. We also show that knocking down Dicer1 and Ago1 mRNAs led to an increased sensitivity to Plasmodium infection. Altogether, these data support an involvement of miRNAs as new layers in the regulation of Anopheles defence reaction.

Published
2007
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11. The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster

Author

Maria-Carla Saleh, Bassam Berry, Catherine K. Foo, Christophe Antoniewski, Raul Andino, Andrew R. Houk, Ronald P. van Rij, University of California [San Francisco] (UC San Francisco), University of California (UC), Biologie du Développement, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was financially supported by the Pasteur Institute and the CNRS, and by a grant from the ARC (#3203) to C.A. and NIH grants AI40085 and AI064738 to R.A., We thank members of the Andino and Pat O'Farrell laboratory for discussions, technical support, and advice on fly work. We thank O. Voinnet and J.L. Imler for helpful discussions. We thank Judith Frydman and Annemieke Jansens for critical reading the manuscript. Peter Sarnow and Sarah Cherry kindly provided DCV and CrPV virus stocks. We are grateful to C. Vaury for the gift of the B2 DNA, and to D. Fagegaltier, L. Röder, E. Georgenthum, and the BestGene, Inc., for generating transgenic flies. Armin Hekele prepared some of the dsRNA used in this study. We thank Richard Carthew for providing the GMR-wIR fly stock, and Phil Zamore for providing fly RNAi mutants and experimental advice on the Dicer assays in S2 cell extracts. B.B. is a Lebanese CNRSL fellow., University of California [San Francisco] (UCSF), University of California, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)

Subjects
Ribonuclease III, Small interfering RNA, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Suppression, Genetic, MESH: Argonaute Proteins, MESH: Ribonuclease III, RNA interference, Drosophila Proteins, MESH: Animals, MESH: Gene Silencing, MESH: Suppression, Genetic, 0303 health sciences, MESH: RNA Helicases, 030302 biochemistry & molecular biology, Cricket Paralysis virus, Argonaute, 3. Good health, RNA silencing, Drosophila melanogaster, Drosophila C virus, MESH: RNA, Viral, Argonaute Proteins, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, [SDV.IMM]Life Sciences [q-bio]/Immunology, RNA Interference, RNA Helicases, Research Paper, dsRNA-binding domain, RNA-induced silencing complex, MESH: Drosophila Proteins, Trans-acting siRNA, MESH: RNA Interference, Insect Viruses, Biology, MESH: Drosophila melanogaster, Viral Proteins, 03 medical and health sciences, MESH: RNA, Double-Stranded, Antiviral defense, Genetics, Animals, RNA-Induced Silencing Complex, RasiRNA, RNAi suppressor, Gene Silencing, RNA, Double-Stranded, 030304 developmental biology, fungi, MESH: Insect Viruses, MESH: RNA-Induced Silencing Complex, biology.organism_classification, Virology, MESH: Viral Proteins, Developmental Biology
Abstract

Most organisms have evolved defense mechanisms to protect themselves from viruses and other pathogens. Arthropods lack the protein-based adaptive immune response found in vertebrates. Here we show that the central catalytic component of the RNA-induced silencing complex (RISC), the nuclease Argonaute 2 (Ago-2), is essential for antiviral defense in adult Drosophila melanogaster. Ago-2-defective flies are hypersensitive to infection with a major fruit fly pathogen, Drosophila C virus (DCV), and with Cricket Paralysis virus (CrPV). Increased mortality in ago-2 mutant flies was associated with a dramatic increase in viral RNA accumulation and virus titers. The physiological significance of this antiviral mechanism is underscored by our finding that DCV encodes a potent suppressor of RNA interference (RNAi). This suppressor binds long double-stranded RNA (dsRNA) and inhibits Dicer-2-mediated processing of dsRNA into short interfering RNA (siRNA), but does not bind short siRNAs or disrupt the microRNA (miRNA) pathway. Based on these results we propose that RNAi is a major antiviral immune defense mechanism in Drosophila.

Published
2006
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12. The chromatoid body of male germ cells: similarity with processing bodies and presence of Dicer and microRNA pathway components

Author

Martti Parvinen, Suvendra N. Bhattacharyya, Sarah Kimmins, Noora Kotaja, Witold Filipowicz, Paolo Sassone-Corsi, Lukasz Jaskiewicz, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, and Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Ribonuclease III, Cytoplasm, Somatic cell, Cellular differentiation, DEAD-box RNA Helicases, Mice, 0302 clinical medicine, MESH: Ribonuclease III, Chlorocebus aethiops, MESH: Gene Expression Regulation, Developmental, MESH: Animals, MESH: Proteins, 0303 health sciences, Multidisciplinary, biology, MESH: RNA Helicases, MESH: Spermatozoa, Gene Expression Regulation, Developmental, Cell Differentiation, Biological Sciences, Argonaute, Spermatozoa, RNA Helicase A, Chromatin, Cell biology, MESH: COS Cells, medicine.anatomical_structure, Argonaute Proteins, COS Cells, RNA Helicases, Germ cell, MESH: Cell Differentiation, MESH: Chromatin, 03 medical and health sciences, microRNA, medicine, Animals, MESH: DEAD-box RNA Helicases, MESH: Mice, 030304 developmental biology, MESH: Cytoplasm, Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Molecular biology, MESH: Cercopithecus aethiops, MESH: Male, MicroRNAs, biology.protein, Chromatoid body, MESH: MicroRNAs, 030217 neurology & neurosurgery, Dicer
Abstract

International audience; The chromatoid body is a perinuclear, cytoplasmic cloud-like structure in male germ cells whose function has remained elusive. Here we show that the chromatoid body is related to the RNA-processing body of somatic cells. Dicer and components of microRNP complexes (including Ago proteins and microRNAs) are highly concentrated in chromatoid bodies. Furthermore, we show that Dicer interacts with a germ cell-specific chromatoid body component, the RNA helicase MVH (mouse VASA homolog). Thus, chromatoid bodies seem to operate as intracellular nerve centers of the microRNA pathway. Our findings underscore the importance of posttranscriptional gene regulation and of the microRNA pathway in the control of postmeiotic male germ cell differentiation.

Published
2006
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