RNA Polymerase II Transcription Elongation Control

Guo, Jiannan; Price, David H.

doi:10.1021/cr400105n

Cited by 108 publications

(145 citation statements)

References 416 publications

(751 reference statements)

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“…1) results in an inhibition of elongation that is qualitatively very similar to the well known inhibition of P-TEFb-dependent elongation by flavopiridol and 5,6-Dichlorobenzimidazole riboside (62). Epistatic assays also show that OGA activity is part of a sequence of enzymatic activities in vitro: CDK7/TFIIH activity, followed by P-TEFb activity, followed by OGA activity (Fig.…”

Section: Discussionsupporting

confidence: 73%

“…2), a component of the elongation machinery, further suggests that the relationship between the regulation of O-GlcNAcylation and elongation is a bone fide one. SPT5 is a well known elongation factor required for establishing a paused pol II and, after phosphorylation, promoting productive elongation (62). To our knowledge, SPT5 has only been documented in a complex with SPT4, and we have yet to find any indication of SPT4 in the OEC.…”

Section: Discussionmentioning

confidence: 84%

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O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

Resto

Kim

Fernandez

et al. 2016

Journal of Biological Chemistry

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We describe here the identification and functional characterization of the enzyme O-GlcNAcase (OGA) as an RNA polymerase II elongation factor. Using in vitro transcription elongation assays, we show that OGA activity is required for elongation in a crude nuclear extract system, whereas in a purified system devoid of OGA the addition of rOGA inhibited elongation. Furthermore, OGA is physically associated with the known RNA polymerase II (pol II) pausing/elongation factors SPT5 and TRIM28-KAP1-TIF1␤, and a purified OGA-SPT5-TIF1␤ complex has elongation properties. Lastly, ChIP-seq experiments show that OGA maps to the transcriptional start site/5 ends of genes, showing considerable overlap with RNA pol II, SPT5, TRIM28-KAP1-TIF1␤, and O-GlcNAc itself. These data all point to OGA as a component of the RNA pol II elongation machinery regulating elongation genome-wide. Our results add a novel and unexpected dimension to the regulation of elongation by the insertion of O-GlcNAc cycling into the pol II elongation regulatory dynamics.RNA polymerase II is the species of polymerase that transcribes the protein-coding genes in the cell. Largely based on in vitro transcription data and bacterial transcriptional regulation, it was thought that the pathway of transcription initiation was the de novo assembly and recruitment of general factors and pol II 4 into a preinitiation complex at promoters. In other words, transcription was solely controlled by whether initiation occurred or not. However, in the late 1980s, a transcriptionally engaged pol II was found on several genes, located roughly at ϩ50 relative to the transcriptional start site (TSS) (1-3). More recently, genome-wide approaches have shown that paused pol II exists on at least 40% of promoters in the genome (4 -9).These data show that the regulation of elongation is a significant and widespread method by which cells regulate gene expression.Biochemically, the establishment of a paused polymerase requires the recruitment of DSIF and NELF to pol II early in elongation to prevent pol II from productive elongation (10 -13). Release of the paused polymerase is achieved with P-TEFb phosphorylation of DSIF and NELF, ejecting NELF from pol II and converting DSIF into a positive elongation factor (14,15). The more recent discoveries of additional factors likely involved in pause establishment and release include human capping enzyme (16), the TFIIH-associated kinase, CDK7 (17, 18), the TFIIH ERCC3 helicase (19), , Integrator (23,24), ELL (25), TFIIS (26), TRIM28-KAP1-TIF1␤ (27, 28), Top1 (29), SEC (30), PAF complex (31, 32), and Gdown1 (33). The plethora of factors suggests that more complicated dynamics are at play in regulating pausing and elongation. Additionally, it is not clear, and indeed difficult to know, whether all of the factors involved in pol II pausing and elongation have been identified. This difficulty is due mostly to the absence of a human cell-based in vitro transcription system that recapitulates a paused polymerase and with which the full complement of...

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 84%

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

Resto

Kim

Fernandez

et al. 2016

Journal of Biological Chemistry

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“…This pausing keeps these promoters available for rapid induction by P-TEFb, whose activity causes NELF to dissociate and RNAPII and DSIF to elongate on the gene (26,27,30,31). To confirm which promoter was responsible for the observed P-TEFb-sensitive HEXIM1 transcription, ChIP-Seq was performed with anti-RNAPII, anti-NELF-A (NELF), and anti-SPT5 (DSIF) antibodies in HeLa cells.…”

Section: Chip-seq Data Confirm the Existence Of The P-tefb-induciblementioning

confidence: 99%

Release of Positive Transcription Elongation Factor b (P-TEFb) from 7SK Small Nuclear Ribonucleoprotein (snRNP) Activates Hexamethylene Bisacetamide-inducible Protein (HEXIM1) Transcription

Liu

Xiang

Fujinaga

et al. 2014

Journal of Biological Chemistry

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“…128 In summary, evolutionary conservation of NELF correlates with widespread Pol II pausing in many eukaryotes. 64 …”

Section: Pol II Elongation Control: a Cdk-9-mediated Transition In Mementioning

confidence: 99%

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

Bowman

Kelly

2014

Nucleus

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RNA Polymerase II Transcription Elongation Control

Cited by 108 publications

References 416 publications

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

O-GlcNAcase Is an RNA Polymerase II Elongation Factor Coupled to Pausing Factors SPT5 and TIF1β

Release of Positive Transcription Elongation Factor b (P-TEFb) from 7SK Small Nuclear Ribonucleoprotein (snRNP) Activates Hexamethylene Bisacetamide-inducible Protein (HEXIM1) Transcription

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

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