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

Autor: Laura Milligan, Camille Sayou, Alex Tuck, Tatsiana Auchynnikava, Jane EA Reid, Ross Alexander, Flavia de Lima Alves, Robin Allshire, Christos Spanos, Juri Rappsilber, Jean D Beggs, Grzegorz Kudla, David Tollervey
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: eLife, Vol 6 (2017)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.27082
Popis: 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 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.
Databáze: Directory of Open Access Journals