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

TY - JOUR

T1 - The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription

AU - Akay, Alper

AU - Di Domenico, Tomas

AU - Suen, Kin M.

AU - Nabih, Amena

AU - Parada, Guillermo E.

AU - Larance, Mark

AU - Medhi, Ragini

AU - Berkyurek, Ahmet C.

AU - Zhang, Xinlian

AU - Wedeles, Christopher J.

AU - Rudolph, Konrad L.M.

AU - Engelhardt, Jan

AU - Hemberg, Martin

AU - Ma, Ping

AU - Lamond, Angus I.

AU - Claycomb, Julie M.

AU - Miska, Eric A.

N1 - 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.

PY - 2017/8/7

Y1 - 2017/8/7

N2 - 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.

AB - 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.

KW - C. elegans

KW - epigenetic inheritance

KW - nuclear RNAi

KW - piRNA

KW - Piwi

KW - RNA processing

KW - RNAi

KW - splicing

KW - transcription

KW - transposable elements

U2 - 10.1016/j.devcel.2017.07.002

DO - 10.1016/j.devcel.2017.07.002

M3 - Article

C2 - 28787591

AN - SCOPUS:85026503930

SN - 1534-5807

VL - 42

SP - 241-255.e6

JO - Developmental Cell

JF - Developmental Cell

IS - 3

ER -