Antisense transcription licenses nascent transcripts to mediate transcriptional gene silencing
- 1Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA;
- 2State Key Laboratory of Agricultural Microbiology, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China;
- 3State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, ZhongGuanCun, Beijing 100080, China
- Corresponding author: yi.liu{at}utsouthwestern.edu
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↵4 These authors contributed equally to this work.
Abstract
In eukaryotes, antisense transcription can regulate sense transcription by induction of epigenetic modifications. We showed previously that antisense transcription triggers Dicer-independent siRNA (disiRNA) production and disiRNA locus DNA methylation (DLDM) in Neurospora crassa. Here we show that the conserved exonuclease ERI-1 (enhanced RNAi-1) is a critical component in this process. Antisense transcription and ERI-1 binding to target RNAs are necessary and sufficient to trigger DLDM. Convergent transcription causes stalling of RNA polymerase II during transcription, which permits ERI-1 to bind nascent RNAs in the nucleus and recruit a histone methyltransferase complex that catalyzes chromatin modifications. Furthermore, we show that, in the cytoplasm, ERI-1 targets hundreds of transcripts from loci without antisense transcription to regulate RNA stability. Together, our results demonstrate a critical role for transcription kinetics in long noncoding RNA-mediated epigenetic modifications and identify ERI-1 as an important regulator of cotranscriptional gene silencing and post-transcriptional RNA metabolism.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.285791.116.
- Received June 17, 2016.
- Accepted October 21, 2016.
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