title: Antisense transcription licenses nascent transcripts to mediate transcriptional gene silencing.
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.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Yunkun
authors.initials: Y
authors.lastname: Dang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.
authors.forename: Jiasen
authors.initials: J
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, ZhongGuanCun, Beijing 100080, China.
authors.forename: Xianyun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005800:Genes, Fungal / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D009154:Mutation; D009492:Neurospora crassa / Q000235:genetics*; D011485:Protein Binding; D020871:RNA Stability / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D006657:Histones; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D005092:Exonucleases
keywords: DNA methylation; Neurospora; antisense transcription; gene silencing; small RNA