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

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

来源：Developmental Cell, 2017, 42(3): 241-+.

DOI：10.1016/j.devcel.2017.07.002

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.

• 出版日期2017-8-7
• 单位上海生物信息技术研究中心