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

Autor: Akay, A, Di Domenico, T, Suen, KM, Nabih, A, Parada, GE, Larance, M, Medhi, R, Berkyurek, AC, Zhang, X, Wedeles, CJ, Rudolph, KLM, Engelhardt, J, Hemberg, M, Ma, P, Lamond, AI, Claycomb, JM, Miska, EA
Přispěvatelé: Akay, Alper [0000-0001-6825-4443], Di Domenico, Tomas [0000-0003-2887-815X], Medhi, Ragini [0000-0002-2780-0708], Rudolph, Konrad [0000-0002-9866-7051], Miska, Eric [0000-0002-4450-576X], Apollo - University of Cambridge Repository
Rok vydání: 2017
Předmět:
Zdroj: Developmental Cell
ISSN: 1534-5807
DOI: 10.1016/j.devcel.2017.07.002
Popis: Summary 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.
Graphical Abstract
Highlights • Nuclear Argonaute HRDE-1 physically interacts with the helicase EMB-4/AQR • EMB-4/AQR is required for heritable silencing of genes and transposable elements • Intronic sequences form a barrier to nuclear RNAi pathway • EMB-4/AQR removes intronic barriers for efficient silencing by HRDE-1
Nuclear RNAi is essential for heritable silencing in many organisms. Akay et al. show that RNA helicase EMB-4/AQR physically interacts with nuclear Argonaute HRDE-1 and bridges the small RNA pathway to transcriptional silencing. They further show that introns can form a barrier to transcriptional silencing, which EMB-4/AQR can overcome.
Databáze: OpenAIRE
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