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
Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
Dev Cell. 2017 Aug 7;42(3):241-255.e6. 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.
小RNA在基因组抵御转座元件的过程中发挥着关键作用，并引导AGO蛋白与新生RNA转录本结合，从而诱导共转录基因沉默。然而，这一过程的分子基础仍然未知。在此，我们鉴定出保守的RNA解旋酶水瓶座/EMB-4是秀丽隐杆线虫中小RNA通路与转录机制之间的直接且必要的联系。水瓶座与生殖系AGO蛋白HRDE-1发生物理相互作用。启动小RNA诱导的可遗传基因沉默需要水瓶座。HRDE-1和水瓶座沉默重叠的基因和转座元件集。令人惊讶的是，从靶基因中去除内含子消除了小RNA依赖性基因沉默对水瓶座的需求，但对HRDE-1没有影响。我们得出结论，水瓶座允许小RNA通路竞争进入正在进行共转录剪接的新生转录本，以便检测并沉默转座元件。因此，水瓶座和HRDE-1作为协调基因表达和基因组防御的守门人。
