RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination of the catalytic subunit.

Elife 2017 10 13;6. Epub 2017 Oct 13.

Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland.

Numerous links exist between co-transcriptional RNA processing and the transcribing RNAPII. In particular, pre-mRNA splicing was reported to be associated with slowed RNAPII elongation. Here, we identify a site of ubiquitination (K1246) in the catalytic subunit of RNAPII close to the DNA entry path. Ubiquitination was increased in the absence of the Bre5-Ubp3 ubiquitin protease complex. Bre5 binds RNA in vivo, with a preference for exon 2 regions of intron-containing pre-mRNAs and poly(A) proximal sites. Ubiquitinated RNAPII showed similar enrichment. The absence of Bre5 led to impaired splicing and defects in RNAPII elongation in vivo on a splicing reporter construct. Strains expressing RNAPII with a KR mutation showed reduced co-transcriptional splicing. We propose that ubiquinitation of RNAPII is induced by RNA processing events and linked to transcriptional pausing, which is released by Bre5-Ubp3 associated with the nascent transcript.

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http://dx.doi.org/10.7554/eLife.27082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673307PMC
October 2017

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