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A novel model of THO/TREX loading onto target RNAs in metazoan gene expression
Junho K. Hur1, Yun Doo Chung2,*
1Center for Genome Engineering, Institute for Basic Science, Seoul, Korea,
2Department of Life Science, University of Seoul, Seoul, Korea
Abstract
The THO/TREX complex consists of several conserved subunits and is required for mRNA export. In metazoans THO/TREX binds a subset of mRNAs during RNA splicing, and facilitates nuclear export of them. How THO/TREX selects RNA targets has, however, not been completely understood. In our recent study, we reported that THO is loaded onto Piwi-interacting RNA (piRNA) precursor transcripts independent of splicing and facilitates convergent transcription in Drosophila ovary. The precursors are later processed into mature piRNAs, a small noncoding RNAs that silences transposable elements (TEs). We observed that piRNAs originated from dual-strand clusters, where precursors are transcribed from both strands, were specifically affected by THO mutation. Analysis of THO-bound RNAs showed enrichment of dual-strand transcripts. Interestingly, THO loading onto piRNA precursors was dependent on Cutoff (Cuff), which comprises the Rhino-Deadlock-Cutoff (RDC) complex that is recruited to dual-strand clusters by recognizing H3K9me3 and licenses convergent transcription from the cluster. We also found that THO mutation affected transcription from dual-strand clusters. Together, we concluded that THO/TREX is recruited to dual-strand piRNA clusters, independent of splicing event, via multi-protein interactions with chromatin structure. Then it facilitates transcription probably by suppressing premature termination to ensure piRNA precursors are expressed adequately.
Abstract, Accepted Manuscript(in press) [Submitted on June 15, 2016, Accepted on June 16, 2016]
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