The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription

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Suen, KM 
Nabih, A 
Parada, GE 

Small RNAs play a crucial role in genome defense against transposable elements and guide Argonaute proteins to nascent RNA transcripts to induce co-transcriptional gene silencing. However, the molecular basis of this process remains unknown. Here, we identify the conserved RNA helicase Aquarius/EMB-4 as a direct and essential link between small RNA pathways and the transcriptional machinery in Caenorhabditis elegans. Aquarius physically interacts with the germline Argonaute HRDE-1. Aquarius is required to initiate small-RNA-induced heritable gene silencing. HRDE-1 and Aquarius silence overlapping sets of genes and transposable elements. Surprisingly, removal of introns from a target gene abolishes the requirement for Aquarius, but not HRDE-1, for small RNA-dependent gene silencing. We conclude that Aquarius allows small RNA pathways to compete for access to nascent transcripts undergoing co-transcriptional splicing in order to detect and silence transposable elements. Thus, Aquarius and HRDE-1 act as gatekeepers coordinating gene expression and genome defense.

C. elegans, Piwi, RNA processing, RNAi, epigenetic inheritance, nuclear RNAi, piRNA, splicing, transcription, transposable elements, Animals, Argonaute Proteins, Caenorhabditis elegans, Caenorhabditis elegans Proteins, DNA Transposable Elements, Introns, Nuclear Proteins, Protein Binding, RNA Interference
Journal Title
Developmental Cell
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Journal ISSN
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Cancer Research Uk (None)
Cancer Research UK (18583)
Wellcome Trust (104640/Z/14/Z)
Wellcome Trust (092096/Z/10/Z)
European Research Council (260688)
Cancer Research Uk (None)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (747666)
A.C.B. was supported by an HFSP grant to E.A.M. (RPG0014/2015). This work was supported by Cancer Research UK (C13474/A18583, C6946/A14492), the Wellcome Trust (104640/Z/14/Z, 092096/Z/10/Z), and The European Research Council (ERC, grant 260688). The work of P.M. and X.Z. is supported by NIH grant R01GM113242 and NIH grant R01GM122080. R.M. was a Commonwealth Scholar, funded by the UK Government. J.M.C., A.N., and C.J.W. were supported by the CIHR (MOP-274660) and the Canada Research Chairs Program. A.I.L. was supported by a Wellcome Trust Programme Grant (108058/Z/15/Z) and M.L was supported by 2013/RSE/SCOTGOV/ MARIECURIE.