ZWC complex-mediated SPT5 phosphorylation suppresses divergent antisense RNA transcription at active gene promoters.
Nucleic Acids Res
; 50(7): 3835-3851, 2022 04 22.
Article
in En
| MEDLINE
| ID: mdl-35325203
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription, Genetic
/
Nuclear Proteins
/
Chromosomal Proteins, Non-Histone
/
RNA, Antisense
/
Transcriptional Elongation Factors
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2022
Type:
Article
Affiliation country:
South Korea