RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination of the catalytic subunit
Open accessAbstract
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.
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This pausing is enforced by ubiquitylation of the catalytic subunit of RNA Pol II.
“Finally, this pausing is enforced by ubiquitylation of the catalytic subunit of RNA Pol II (Milligan et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Milligan et al, 2017
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References 70 · Cited by 23
- Authors
- Milligan, L., Sayou, C., Tuck, A., Auchynnikava, T., Reid, J. E., Alexander, R., Alves, F. D. L., Allshire, R., Spanos, C., Rappsilber, J., Beggs, J. D., Kudla, G., & Tollervey, D.
- Affiliations
- Wellcome Centre for Cell Biology (GB)
- Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, Scotland
- Western General Hospital (GB)
- Corresponding author
- Tollervey, David
- ORCID
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2017-10-13
- Volume
- 6
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC5673307
- OpenAlex
- W2762563319
- Cited by
- 23
- References
- 70
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Wellcome (109916, 104648, 108504, 093853, 097383, 092076, 200885)
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- RNA polymerase II, ubiquitination, pre-mRNA splicing, co-transcriptional splicing, transcriptional pausing, RNA polymerase II elongation, nascent RNA, exon 2, Saccharomyces cerevisiae
- MeSH terms
- Models, Biological, Endopeptidases, RNA Polymerase II, RNA Precursors, Mutation, Missense, Catalytic Domain, Saccharomyces cerevisiae Proteins, Mutant Proteins, Ubiquitination
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