5 years ago

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

Juri Rappsilber, Jane E A Reid, Tatsiana Auchynnikava, David Tollervey, Ross Alexander, Robin Allshire, Alex Tuck, Laura Milligan, Camille Sayou, Christos Spanos, Jean D Beggs, Grzegorz Kudla, Flavia de Lima Alves
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 K1246R mutation showed reduced cotranscriptional 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.

Publisher URL: https://elifesciences.org/articles/27082

DOI: 10.7554/eLife.27082

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