title: Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila.
abstract: The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis.
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Junho K
authors.initials: JK
authors.lastname: Hur
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Life Science, University of Seoul, Seoul 130-743, Korea.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Moon
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Maria
authors.initials: M
authors.lastname: Ninova
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Georgi K
authors.initials: GK
authors.lastname: Marinov
authors.affiliation: Department of Life Science, University of Seoul, Seoul 130-743, Korea.
authors.forename: Yun D
authors.initials: YD
authors.lastname: Chung
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Alexei A
authors.initials: AA
authors.lastname: Aravin
mesh_terms: D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D008297:Male; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012322:RNA Precursors / Q000378:metabolism; D034741:RNA, Small Interfering / Q000096:biosynthesis* / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: C000590395:Cuff protein, Drosophila; D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D012322:RNA Precursors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C583488:THOC5 protein, Drosophila
keywords: TREX; Thoc5; mRNA loading; piRNA biogenesis; transcriptional regulation