Sub1 associates with Spt5 and influences RNA polymerase II transcription elongation rate

García, Alicia; Collin, Alejandro; Calvo, Olga

doi:10.1091/mbc.e12-04-0331

Cited by 26 publications

(79 citation statements)

References 80 publications

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“…These genetic data prompted us to hypothesize that the sub1 ∆ strain might exhibit a slow elongation rate, which was confirmed by Garcia, et al while the work by Braberg, et al was under review: RNAPII elongates slowly on the GAL1 gene in the absence of SUB1 51 . Consistent with our predictions, the sub1 ∆ strain exhibited improved splicing at a large number of genes, similar to what is observed in slow RNAPII mutant strains.…”

Section: How Might Kinetic Coupling Occur In S Cerevisiae?supporting

confidence: 87%

Adventures in time and space

et al. 2014

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Control of pre-mRNA splicing is a critical part of the eukaryotic gene expression process. Extensive evidence indicates that transcription and splicing are spatiotemporally coordinated and that most splicing events occur co-transcriptionally. A kinetic coupling model has been proposed in metazoans to describe how changing RNA Polymerase II (RNAPII) elongation rate can impact which alternative splice sites are used. In Saccharomyces cerevisiae, in which most spliced genes have only a single intron and splice sites adhere to a strong consensus sequence, we recently observed that splicing efficiency was sensitive to mutations in RNAPII that increase or decrease its elongation rate. Our data revealed that RNAPII speed and splicing efficiency are generally anti-correlated: at many genes, increased elongation rate caused decreased splicing efficiency, while decreased elongation rate increased splicing efficiency. An improved splicing phenotype was also observed upon deletion of SUB1, a condition in which elongation rate is slowed. We discuss these data in the context of a growing field and expand the kinetic coupling model to apply to both alternative splicing and splicing efficiency.

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Section: How Might Kinetic Coupling Occur In S Cerevisiae?supporting

confidence: 87%

Adventures in time and space

et al. 2014

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“…The epistatic relationships between fast RNAPII alleles and sub1Δ suggest that Sub1 activity may be bypassed when RNAPII catalytic activity is increased. Collectively, our data indicate that Sub1 plays a direct role in transcriptional initiation and influences mRNA splicing, possibly via its effect on elongation (García et al, 2012). …”

Section: Discussionmentioning

confidence: 78%

“…We focused on genes that behaved as positively acting factors and observed that sub1Δ had the strongest pattern in this regard. Interestingly, previous evidence has implicated Sub1 as a positive factor in in vitro transcription assays (reviewed in Conesa and Acker, 2010), as well as in vivo (García et al, 2012). The genetic relationships from the pE-MAP were confirmed using standard growth assays in which sub1Δ exacerbated slow RNAPII alleles (Figure 7B) and partially suppressed fast RNAPII alleles (Figure 7C).…”

Section: Resultsmentioning

confidence: 99%

From Structure to Systems: High-Resolution, Quantitative Genetic Analysis of RNA Polymerase II

Braberg

Jin

Moehle

et al. 2013

Cell

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SUMMARY RNA polymerase II (RNAPII) lies at the core of dynamic control of gene expression. Using 53 RNAPII point mutants, we generated a point mutant epistatic miniarray profile (pE-MAP) comprising ~60,000 quantitative genetic interactions in Saccharomyces cerevisiae. This analysis enabled functional assignment of RNAPII subdomains and uncovered connections between individual regions and other protein complexes. Using splicing microarrays and mutants that alter elongation rates in vitro, we found an inverse relationship between RNAPII speed and in vivo splicing efficiency. Furthermore, the pE-MAP classified fast and slow mutants that favor upstream and downstream start site selection, respectively. The striking coordination of polymerization rate with transcription initiation and splicing suggests that transcription rate is tuned to regulate multiple gene expression steps. The pE-MAP approach provides a powerful strategy to understand other multifunctional machines at amino acid resolution.

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“…Sub1 interacts with RNA polymerase II 24,25 and III 26 and plays an essential regulatory role in transcription initiation, elongation, and mRNA 3’-end formation 24,27,28 . We therefore tested whether Sub1 can bind to a G4 region on chromosomal DNA in vivo .…”

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confidence: 99%