1. Small-RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants
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Blaise Li, Martino Ugolini, Damarys Loew, Germano Cecere, Aleksei Samolygo, Céline Didier, Eric Cornes, Meetali Singh, Giorgia Barucci, Piergiuseppe Quarato, Florent Dingli, Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Scuola Normale Superiore di Pisa (SNS), Moscow Institute of Physics and Technology [Moscow] (MIPT), Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie [Paris], This project has received funding from the Institut Pasteur, the CNRS and the European Research Council (ERC) under the EU Horizon 2020 research and innovation programme under grant agreement no. ERC-StG- 679243. G.B. is part of the Pasteur–Paris University (PPU) International PhD Program and has received funding from the EU Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 665807. E.C. was supported by a Pasteur-Cantarini Fellowship program. F.D. and D.L. have received funding from Région Ile-de-France and Fondation pour la Recherche Médicale grants to support this study, We thank the members of the Cecere laboratory, D. Canzio, N. Iovino, R. Sawarkar and P. Andersen for discussions of the manuscript, the Miska, the Mello, the Kennedy, the Seydoux, the Claycomb, the Strome and the Dumont laboratories for sharing strains and/or antibodies. Some strains were provided by the CGC, funded by NIH Office of Research Infrastructure Programs (P40 OD010440)., and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
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MESH: Gene Editing ,MESH: CRISPR-Cas Systems ,Small RNA ,MESH: Argonaute Proteins / deficiency ,MESH: Caenorhabditis elegans Proteins / metabolism ,Inheritance Patterns ,MESH: RNA, Small Interfering / genetics ,MESH: Argonaute Proteins / metabolism ,medicine.disease_cause ,MESH: RNA, Antisense / genetics ,MESH: Argonaute Proteins / genetics ,Animals, Genetically Modified ,Histones ,0302 clinical medicine ,MESH: Histones / metabolism ,MESH: Animals ,RNA, Small Interfering ,MESH: Caenorhabditis elegans / genetics ,Caenorhabditis elegans ,Gene Editing ,0303 health sciences ,Mutation ,MESH: RNA, Messenger / metabolism ,[SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE] ,Biological Evolution ,Cell biology ,Histone ,MESH: Fertility / genetics ,030220 oncology & carcinogenesis ,Argonaute Proteins ,Piwi RNAs ,MESH: RNA, Messenger / genetics ,MESH: Gene Silencing ,Epigenetic memory ,endocrine system ,MESH: Mutation ,MESH: Caenorhabditis elegans / metabolism ,Piwi-interacting RNA ,MESH: Biological Evolution ,Biology ,Article ,MESH: Animals, Genetically Modified ,03 medical and health sciences ,medicine ,Animals ,Gene silencing ,RNA, Antisense ,Gene Silencing ,RNA, Messenger ,MESH: RNA, Antisense / metabolism ,Caenorhabditis elegans Proteins ,Gene ,Repetitive Sequences, Nucleic Acid ,030304 developmental biology ,MESH: RNA, Small Interfering / metabolism ,MESH: Repetitive Sequences, Nucleic Acid ,MESH: Histones / genetics ,urogenital system ,RNA ,Cell Biology ,biology.organism_classification ,Fertility ,RNAi ,biology.protein ,MESH: Caenorhabditis elegans Proteins / genetics ,MESH: Inheritance Patterns ,CRISPR-Cas Systems - Abstract
International audience; PIWI-interacting RNAs (piRNAs) promote fertility in many animals. However, whether this is due to their conserved role in repressing repetitive elements (REs) remains unclear. Here, we show that the progressive loss of fertility in Caenorhabditis elegans lacking piRNAs is not caused by derepression of REs or other piRNA targets but, rather, is mediated by epigenetic silencing of all of the replicative histone genes. In the absence of piRNAs, downstream components of the piRNA pathway relocalize from germ granules and piRNA targets to histone mRNAs to synthesize antisense small RNAs (sRNAs) and induce transgenerational silencing. Removal of the downstream components of the piRNA pathway restores histone mRNA expression and fertility in piRNA mutants, and the inheritance of histone sRNAs in wild-type worms adversely affects their fertility for multiple generations. We conclude that sRNA-mediated silencing of histone genes impairs the fertility of piRNA mutants and may serve to maintain piRNAs across evolution.
- Published
- 2020
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