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The Helicase Aquarius/EMB-4 Is Required to Overcome Intronic Barriers to Allow Nuclear RNAi Pathways to Heritably Silence Transcription.
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.
Afiliación
  • Akay 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.
  • Di Domenico T; 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.
  • Suen KM; 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.
  • Nabih A; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Parada GE; Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
  • Larance M; Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
  • Medhi R; 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.
  • Berkyurek AC; 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.
  • Zhang X; Department of Statistics, University of Georgia, Athens, GA 30602, USA.
  • Wedeles CJ; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Rudolph KLM; 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.
  • Engelhardt J; Bioinformatics Group, Department of Computer Science, Interdisciplinary Center for Bioinformatics, University of Leipzig, Haertelstraße 16-18, Leipzig 04107, Germany.
  • Hemberg M; Wellcome Trust Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, UK.
  • Ma P; Department of Statistics, University of Georgia, Athens, GA 30602, USA.
  • Lamond AI; Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
  • Claycomb JM; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
  • Miska EA; 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. Electr
Dev Cell ; 42(3): 241-255.e6, 2017 08 07.
Article en En | MEDLINE | ID: mdl-28787591
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Nucleares / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans / Interferencia de ARN / Proteínas Argonautas Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Nucleares / Caenorhabditis elegans / Proteínas de Caenorhabditis elegans / Interferencia de ARN / Proteínas Argonautas Límite: Animals Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos