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

Developmental cell | 2017

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.

Pubmed ID: 28787591 RIS Download

Associated grants

  • Agency: European Research Council, International
    Id: 260688
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM122080
  • Agency: Cancer Research UK, United Kingdom
    Id: C13474/A18583
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM113242
  • Agency: Cancer Research UK, United Kingdom
    Id: C6946/A14492
  • Agency: Wellcome Trust, United Kingdom
    Id: 108058/Z/15/Z
  • Agency: Wellcome Trust, United Kingdom
    Id: 104640/Z/14/Z
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 092096/Z/10/Z
  • Agency: Cancer Research UK, United Kingdom
    Id: 11832
  • Agency: CIHR, Canada
    Id: MOP-274660

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