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      Small RNA-mediated transgenerational silencing of histone genes impairs fertility in piRNA mutants

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          Abstract

          PIWI-interacting RNAs (piRNAs) promote fertility in many animals. Yet, 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 mediated by the epigenetic silencing of all 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 the sRNA-mediated silencing of histone genes impairs fertility of piRNA mutants and may serve to maintain piRNAs across evolution.

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          Integration of biological networks and gene expression data using Cytoscape.

          Melissa Cline, Michael Smoot, Ethan Cerami … (2007)
          Cytoscape is a free software package for visualizing, modeling and analyzing molecular and genetic interaction networks. This protocol explains how to use Cytoscape to analyze the results of mRNA expression profiling, and other functional genomics and proteomics experiments, in the context of an interaction network obtained for genes of interest. Five major steps are described: (i) obtaining a gene or protein network, (ii) displaying the network using layout algorithms, (iii) integrating with gene expression and other functional attributes, (iv) identifying putative complexes and functional modules and (v) identifying enriched Gene Ontology annotations in the network. These steps provide a broad sample of the types of analyses performed by Cytoscape.
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            PIWI-interacting RNAs: small RNAs with big functions

            Deniz M Özata, Ildar V. Gainetdinov, Ansgar Zoch … (2018)
            In animals, PIWI-interacting RNAs (piRNAs) of 21-35 nucleotides in length silence transposable elements, regulate gene expression and fight viral infection. piRNAs guide PIWI proteins to cleave target RNA, promote heterochromatin assembly and methylate DNA. The architecture of the piRNA pathway allows it both to provide adaptive, sequence-based immunity to rapidly evolving viruses and transposons and to regulate conserved host genes. piRNAs silence transposons in the germ line of most animals, whereas somatic piRNA functions have been lost, gained and lost again across evolution. Moreover, most piRNA pathway proteins are deeply conserved, but different animals employ remarkably divergent strategies to produce piRNA precursor transcripts. Here, we discuss how a common piRNA pathway allows animals to recognize diverse targets, ranging from selfish genetic elements to genes essential for gametogenesis.
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              Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans.

              J. Graham Ruby, Calvin Jan, Christopher Player … (2006)
              We sequenced approximately 400,000 small RNAs from Caenorhabditis elegans. Another 18 microRNA (miRNA) genes were identified, thereby extending to 112 our tally of confidently identified miRNA genes in C. elegans. Also observed were thousands of endogenous siRNAs generated by RNA-directed RNA polymerases acting preferentially on transcripts associated with spermatogenesis and transposons. In addition, a third class of nematode small RNAs, called 21U-RNAs, was discovered. 21U-RNAs are precisely 21 nucleotides long, begin with a uridine 5'-monophosphate but are diverse in their remaining 20 nucleotides, and appear modified at their 3'-terminal ribose. 21U-RNAs originate from more than 5700 genomic loci dispersed in two broad regions of chromosome IV-primarily between protein-coding genes or within their introns. These loci share a large upstream motif that enables accurate prediction of additional 21U-RNAs. The motif is conserved in other nematodes, presumably because of its importance for producing these diverse, autonomously expressed, small RNAs (dasRNAs).
              Article 0 comments Cited 328 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 100890575
                Journal ID (nlm-ta): Nat Cell Biol
                Journal ID (iso-abbrev): Nat. Cell Biol.
                Title: Nature cell biology
                ISSN (Print): 1465-7392
                ISSN (Electronic): 1476-4679
                Publication date Nihms-submitted: 06 January 2020
                Publication date (Electronic): 03 February 2020
                Publication date (Print): February 2020
                Publication date PMC-release: 03 August 2020
                Volume: 22
                Issue: 2
                Pages: 235-245
                Affiliations
                [1 ]Mechanisms of Epigenetic Inheritance, Department of Developmental and Stem Cell Biology, Institut Pasteur, UMR3738, CNRS, Paris, 75015 France
                [2 ]Sorbonne Université, Collège doctoral, F-75005 Paris, France
                [3 ]Bioinformatics and Biostatistics Hub – C3BI, Institut Pasteur, USR 3756, CNRS, Paris, 75015 France
                [4 ]Scuola Normale Superiore, Pisa, Italy
                [5 ]Moscow Institute of Physics and Technology, Moscow, Russia
                [6 ]Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, Paris, France
                Author notes
                [† ]Corresponding author. germano.cecere@ 123456pasteur.fr
                Article
                Manuscript ID: EMS85359
                DOI: 10.1038/s41556-020-0462-7
                PMC ID: 7272227
                PubMed ID: 32015436
                SO-VID: d2fdadde-2286-46f8-92b2-200df3477f3c
                License:

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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                ScienceOpen disciplines: Cell biology
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                ScienceOpen disciplines: Cell biology

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