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Nucleic Acids Res., Published: 23 March 2022 | https://doi.org/10.1093/nar/gkac193 ZWC complex-mediated SPT5 phosphorylation suppresses divergent antisense RNA transcription at active gene promoters

Kihyun Park¹, Jian Zhong², Jin Sung Jang^3,4, Jihyun Kim¹, Hye-Jung Kim⁵, Jeong-Heon Lee^2,4,6,* and Jaehoon Kim^1,*

¹Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea, ²Epigenomics Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA, ³Medical Genome Facility, Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA, ⁴Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA, ⁵New Drug Development Center, OSONG Medical Innovation Foundation, Cheongju 28160, South Korea and ⁶Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA

^*Corresponding author.

Abstract

The human genome encodes large numbers of non-coding RNAs, including divergent antisense transcripts at transcription start sites (TSSs). However, molecular mechanisms by which divergent antisense transcription is regulated have not been detailed. Here, we report a novel ZWC complex composed of ZC3H4, WDR82 and CK2 that suppresses divergent antisense transcription. The ZWC complex preferentially localizes at TSSs of active genes through direct interactions of ZC3H4 and WDR82 subunits with the S5p RNAPII C-terminal domain. ZC3H4 depletion leads to increased divergent antisense transcription, especially at genes that naturally produce divergent antisense transcripts. We further demonstrate that the ZWC complex phosphorylates the previously uncharacterized N-terminal acidic domain of SPT5, a subunit of the transcription-elongation factor DSIF, and that this phosphorylation is responsible for suppressing divergent antisense transcription. Our study provides evidence that the newly identified ZWC-DSIF axis regulates the direction of transcription during the transition from early to productive elongation.

논문정보

형식Research article
게재일2022년 03월 (BRIC 등록일 2022-04-19)
연구진국내(교신)+국외 연구진
분야 생명과학 > 유전자발현

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