RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination

Autoři: Jose F. Victorino aff001;  Melanie J. Fox aff001;  Whitney R. Smith-Kinnaman aff001;  Sarah A. Peck Justice aff001;  Katlyn H. Burriss aff001;  Asha K. Boyd aff001;  Megan A. Zimmerly aff001;  Rachel R. Chan aff001;  Gerald O. Hunter aff001;  Yunlong Liu aff002;  Amber L. Mosley aff001
Působiště autorů: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America aff001;  Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America aff002;  Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, United States of America aff003
Vyšlo v časopise: RNA Polymerase II CTD phosphatase Rtr1 fine-tunes transcription termination. PLoS Genet 16(3): e32767. doi:10.1371/journal.pgen.1008317
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008317


RNA Polymerase II (RNAPII) transcription termination is regulated by the phosphorylation status of the C-terminal domain (CTD). The phosphatase Rtr1 has been shown to regulate serine 5 phosphorylation on the CTD; however, its role in the regulation of RNAPII termination has not been explored. As a consequence of RTR1 deletion, interactions within the termination machinery and between the termination machinery and RNAPII were altered as quantified by Disruption-Compensation (DisCo) network analysis. Of note, interactions between RNAPII and the cleavage factor IA (CF1A) subunit Pcf11 were reduced in rtr1Δ, whereas interactions with the CTD and RNA-binding termination factor Nrd1 were increased. Globally, rtr1Δ leads to decreases in numerous noncoding RNAs that are linked to the Nrd1, Nab3 and Sen1 (NNS) -dependent RNAPII termination pathway. Genome-wide analysis of RNAPII and Nrd1 occupancy suggests that loss of RTR1 leads to increased termination at noncoding genes. Additionally, premature RNAPII termination increases globally at protein-coding genes with a decrease in RNAPII occupancy occurring just after the peak of Nrd1 recruitment during early elongation. The effects of rtr1Δ on RNA expression levels were lost following deletion of the exosome subunit Rrp6, which works with the NNS complex to rapidly degrade a number of noncoding RNAs following termination. Overall, these data suggest that Rtr1 restricts the NNS-dependent termination pathway in WT cells to prevent premature termination of mRNAs and ncRNAs. Rtr1 facilitates low-level elongation of noncoding transcripts that impact RNAPII interference thereby shaping the transcriptome.

Klíčová slova:

Messenger RNA – Non-coding RNA sequences – Phosphatases – RNA sequencing – Transcriptional control – Transcriptional termination – Yeast – ChIP exo


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