A Splicing-Dependent Transcriptional Checkpoint Associated with Prespliceosome Formation
Open accessAbstract
There is good evidence for functional interactions between splicing and transcription in eukaryotes, but how and why these processes are coupled remain unknown. Prp5 protein (Prp5p) is an RNA-stimulated adenosine triphosphatase (ATPase) required for prespliceosome formation in yeast. We demonstrate through in vivo RNA labeling that, in addition to a splicing defect, the prp5-1 mutation causes a defect in the transcription of intron-containing genes. We present chromatin immunoprecipitation evidence for a transcriptional elongation defect in which RNA polymerase that is phosphorylated at Ser5 of the largest subunit's heptad repeat accumulates over introns and that this defect requires Cus2 protein. A similar accumulation of polymerase was observed when prespliceosome formation was blocked by a mutation in U2 snRNA. These results indicate the existence of a transcriptional elongation checkpoint that is associated with prespliceosome formation during cotranscriptional spliceosome assembly. We propose a role for Cus2p as a potential checkpoint factor in transcription.
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Transcriptional pausing over the 3′ splice site is splicing-dependent, since it was lost upon introduction of a mutation in the 5′ or 3′ splice sites.
“This transcriptional pausing over the 3′ splice site is splicing‐dependent, since it was lost upon introduction of a mutation in the 5′ or 3′ splice sites (Alexander et al, 2010; Chathoth et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Chathoth et al, 2014
The Introduction and Discussion (page not provided) describe splicing-dependent Pol II pausing near the intron’s 3′ end, so they support the general point. Our copy does not report that this pausing was lost after a mutation in either the 5′ or 3′ splice site; the mutations studied here affect prespliceosome formation, and the Discussion distinguishes that accumulation from the earlier 3′-end pausing. (LLM, conf=0.84)
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- Authors
- Chathoth, K. T., Barrass, J. D., Webb, S., & Beggs, J. D.
- Affiliations
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Beggs, Jean D.
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 53
- Issue
- 5
- Pages
- 779-790
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC3988880
- OpenAlex
- W2081581101
- Cited by
- 84
- References
- 59
- Citations by year
- 2025: 3 · 2024: 4 · 2023: 3 · 2022: 6 · 2021: 9 · 2020: 8 · 2019: 12 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 12 · 2014: 4
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Molecular Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
- Funders
- Wellcome Trust (087551, 092076)
- 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 › Nuclear Structure and Function
- Keywords
- intron-containing genes, U2 snRNA, Saccharomyces cerevisiae
- MeSH terms
- Adenosine Triphosphate, Exons, Genes, Fungal, Introns, Mutation, Phosphorylation, RNA Polymerase II, RNA Precursors, RNA Splicing, RNA, Small Nuclear, Saccharomyces cerevisiae, Transcription, Genetic, Spliceosomes, Saccharomyces cerevisiae Proteins, Chromatin Immunoprecipitation, DEAD-box RNA Helicases
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