The helicase aquarius/EMB-4 is required to overcome intronic barriers to allow nuclear RNAi pathways to heritably silence transcription

Alper Akay, Tomas Di Domenico, Kin M. Suen, Amena Nabih, Guillermo E. Parada, Mark Larance, Ragini Medhi, Ahmet C. Berkyurek, Xinlian Zhang, Christopher J. Wedeles, Konrad L. M. Rudolph, Jan Engelhardt, Martin Hemberg, Ping Ma, Angus I. Lamond, Julie M. Claycomb, Eric A. Miska

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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.
Original languageEnglish
Pages (from-to)241-255.e6
Number of pages15
JournalDevelopmental Cell
Issue number3
Early online date7 Aug 2017
Publication statusPublished - 7 Aug 2017

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