SAGA Is a General Cofactor for RNA Polymerase II Transcription

Baptista, Tiago; Grünberg, Sebastian; Minoungou, Nadège; Koster, Maria J.E.; Timmers, H. Th. Marc; Hahn, Steven; Devys, Didier; Tora, Làszlò

doi:10.1016/j.molcel.2018.06.007

Cited by 40 publications

(63 citation statements)

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“…The quantitatively similar behavior of SR and RA indicates that global mRNA stability was not appreciably different between the two yeast strains ( Fig EV4). Moreover, supportive of a general role for Mog1 in affecting the transcriptional rate and mRNA abundance, similar effects were observed for transcription of SAGAand TFIID-dominated genes ( Fig 3D), in agreement with the contribution of both SAGA and TFIID to the expression of nearly all yeast genes [55][56][57][58]. These findings led us to the conclusion that Mog1 has a genome-wide impact on RNAPII-transcribed mRNAs.…”

Section: Mog1 Absence Affects H2b Monoubiquitination-dependent Processupporting

confidence: 84%

A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export

et al. 2018

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Monoubiquitination of histone H2B (to H2Bub1) is required for downstream events including histone H3 methylation, transcription, and mRNA export. The mechanisms and players regulating these events have not yet been completely delineated. Here, we show that the conserved Ran‐binding protein Mog1 is required to sustain normal levels of H2Bub1 and H3K4me3 in Saccharomyces cerevisiae. Mog1 is needed for gene body recruitment of Rad6, Bre1, and Rtf1 that are involved in H2B ubiquitination and genetically interacts with these factors. We provide evidence that the absence of MOG1 impacts on cellular processes such as transcription, DNA replication, and mRNA export, which are linked to H2Bub1. Importantly, the mRNA export defect in mog1Δ strains is exacerbated by the absence of factors that decrease H2Bub1 levels. Consistent with a role in sustaining H2Bub and H3K4me3 levels, Mog1 co‐precipitates with components that participate in these modifications such as Bre1, Rtf1, and the COMPASS‐associated factors Shg1 and Sdc1. These results reveal a novel role for Mog1 in H2B ubiquitination, transcription, and mRNA biogenesis.

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Section: Mog1 Absence Affects H2b Monoubiquitination-dependent Processupporting

confidence: 84%

A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export

et al. 2018

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“…Ulp2 and Ubp8 function in the same pathway to control CTD S2-P Recent genome-wide localization studies revealed that the SAGA complex is present on most active genes and the DUB activity of SAGA is detected on almost all yeast genes (Bonnet et al, 2014;Baptista et al, 2017). Furthermore, upon mutation or depletion of SAGA subunits, recruitment of RNAPII even to "TFIID-dominated" genes was significantly impaired, as was synthesis of new mRNA (Bonnet et al, 2014;Baptista et al, 2017). This suggests SAGA is a more general cofactor for RNAPII-mediated transcription than previously thought (Huisinga & Pugh, 2004).…”

Section: Histone Sumoylation Impedes Ctd-s2 Phosphorylationmentioning

confidence: 99%

The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation

Ryu

Wilson-Eisele

et al. 2019

The EMBO Journal

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Many eukaryotic proteins are regulated by modification with the ubiquitin‐like protein small ubiquitin‐like modifier (SUMO). This linkage is reversed by SUMO proteases, of which there are two in Saccharomyces cerevisiae, Ulp1 and Ulp2. SUMO‐protein conjugation regulates transcription, but the roles of SUMO proteases in transcription remain unclear. We report that Ulp2 is recruited to transcriptionally active genes to control local polysumoylation. Mutant ulp2 cells show impaired association of RNA polymerase II (RNAPII) with, and diminished expression of, constitutively active genes and the inducible CUP1 gene. Ulp2 loss sensitizes cells to 6‐azauracil, a hallmark of transcriptional elongation defects. We also describe a novel chromatin regulatory mechanism whereby histone‐H2B ubiquitylation stimulates histone sumoylation, which in turn appears to inhibit nucleosome association of the Ctk1 kinase. Ctk1 phosphorylates serine‐2 (S2) in the RNAPII C‐terminal domain (CTD) and promotes transcript elongation. Removal of both ubiquitin and SUMO from histones is needed to overcome the impediment to S2 phosphorylation. These results suggest sequential ubiquitin‐histone and SUMO‐histone modifications recruit Ulp2, which removes polySUMO chains and promotes RNAPII transcription elongation.

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“…The yeast SAGA complex is a transcriptional coactivator that is involved in transcription of all RNA polymerase II genes [22,23]. Among the SAGA activities are the removal of monoubiquitin from histone H2B, which promotes transcription initiation and elongation [24].…”

Section: Mutation Of Active Site Cysteine To Alanine Increases Affinimentioning

confidence: 99%

Active site alanine mutations convert deubiquitinases into high‐affinity ubiquitin‐binding proteins

et al. 2018

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A common strategy for exploring the biological roles of deubiquitinating enzymes (DUBs) in different pathways is to study the effects of replacing the wild‐type DUB with a catalytically inactive mutant in cells. We report here that a commonly studied DUB mutation, in which the catalytic cysteine is replaced with alanine, can dramatically increase the affinity of some DUBs for ubiquitin. Overexpression of these tight‐binding mutants thus has the potential to sequester cellular pools of monoubiquitin and ubiquitin chains. As a result, cells expressing these mutants may display unpredictable dominant negative physiological effects that are not related to loss of DUB activity. The structure of the SAGA DUB module bound to free ubiquitin reveals the structural basis for the 30‐fold higher affinity of Ubp8C146A for ubiquitin. We show that an alternative option, substituting the active site cysteine with arginine, can inactivate DUBs while also decreasing the affinity for ubiquitin.

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SAGA Is a General Cofactor for RNA Polymerase II Transcription

Cited by 40 publications

References 0 publications

A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export

A role for Mog1 in H2Bub1 and H3K4me3 regulation affecting RNAPII transcription and mRNA export

The Ulp2 SUMO protease promotes transcription elongation through regulation of histone sumoylation

Active site alanine mutations convert deubiquitinases into high‐affinity ubiquitin‐binding proteins

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