Chemical-genomic dissection of the CTD code

Tietjen, Joshua R.; Zhang, David W.; Rodríguez-Molina, Juan B; White, Brent E.; Akhtar, Sohail; Heidemann, Martin; Li, Xin; Chapman, Rob D.; Shokat, Kevan M.; Keleş, Sündüz; Eick, Dirk; Ansari, Aseem Z.

doi:10.1038/nsmb.1900

Cited by 134 publications

(200 citation statements)

References 62 publications

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“…In particular, Ser7 phosphorylation can be found throughout gene bodies in yeast. 12,[21][22][23] However, despite its presence on protein-coding genes, Ser7-P is particularly important for proper transcription of snRNA genes 16 and may or may not be required for transcription or processing of mRNA genes. 16,17 Thus, because Ser2 phosphorylation has the tightest association with transcription elongation regulation, we focus our discussion on the kinases that carry out this modification.…”

Section: The Pol II Ctdmentioning

confidence: 99%

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

Bowman

Kelly

2014

Nucleus

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Section: The Pol II Ctdmentioning

confidence: 99%

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

Bowman

Kelly

2014

Nucleus

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“…Studies in budding yeast, whose RNAPII contains 26 heptarepeats of the consensus CTD sequence, have recently identified gene class-specific CTD phosphorylation patterns and a widespread co-occurrence of such CTD marks at various stages of transcription 18 . Particularly, Ser7 phosphorylation is found early in transcription initiation and retained until transcription termination in all RNAPII-dependent genes.…”

mentioning

confidence: 99%

Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition

2012

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Phosphorylation of RnA polymerase II carboxy-terminal domain (CTD) in hepta-repeats YsPTsPs regulates eukaryotic transcription. Whereas ser5 is phosphorylated in the initiation phase, ser2 phosphorylation marks the elongation state. Here we show that the positive transcription elongation factor P-TEFb is a ser5 CTD kinase that is unable to create ser2/ser5 double phosphorylations, while it exhibits fourfold higher activity on a CTD substrate prephosphorylated at ser7 compared with the consensus hepta-repeat or the YsPTsPK variant. mass spectrometry reveals an equal number of phosphorylations to the number of heptarepeats provided, yet the mechanism of phosphorylation is distributive despite the repetitive nature of the substrate. Inhibition of P-TEFb activity is mediated by two regions in Hexim1 that act synergistically on Cdk9 and Cyclin T1. HIV-1 Tat/TAR abrogates Hexim1 inhibition to stimulate transcription of viral genes but does not change the substrate specificity. Together, these results provide insight into the multifaceted pattern of CTD phosphorylation.

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“…At 3 0 ends of genes, Ser5p levels decrease, presumably by phosphatase action, leaving the CTD phosphorylated at Ser2 to terminate transcription. 17 The CTD phosphorylations enhance maturation of the pre-mRNA by allosteric activation of processing factors 18 and by increasing the concentration of these factors at their site of action. Ser2p is involved in the recruitment of 3 0 end formation factors.…”

Section: Introductionmentioning

confidence: 99%

Localization of RNAPII and 3′ end formation factor CstF subunits onC. elegansgenes and operons

2016

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Transcription termination is mechanistically coupled to pre-mRNA 3 0 end formation to prevent transcription much beyond the gene 3 0 end. C. elegans, however, engages in polycistronic transcription of operons in which 3 0 end formation between genes is not accompanied by termination. We have performed RNA polymerase II (RNAPII) and CstF ChIP-seq experiments to investigate at a genome-wide level how RNAPII can transcribe through multiple poly-A signals without causing termination. Our data shows that transcription proceeds in some ways as if operons were composed of multiple adjacent single genes. Total RNAPII shows a small peak at the promoter of the gene cluster and a much larger peak at 3 0 ends. These 3 0 peaks coincide with maximal phosphorylation of Ser2 within the C-terminal domain (CTD) of RNAPII and maximal localization of the 3 0 end formation factor CstF. This pattern occurs at all 3 0 ends including those at internal sites in operons where termination does not occur. Thus the normal mechanism of 3 0 end formation does not always result in transcription termination. Furthermore, reduction of CstF50 by RNAi did not substantially alter the pattern of CstF64, total RNAPII, or Ser2 phosphorylation at either internal or terminal 3 0 ends. However, CstF50 RNAi did result in a subtle reduction of CstF64 binding upstream of the site of 3 0 cleavage, suggesting that the CstF50/CTD interaction may facilitate bringing the 3 0 end machinery to the transcription complex.

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Chemical-genomic dissection of the CTD code

Cited by 134 publications

References 62 publications

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

RNA Polymerase II transcription elongation and Pol II CTD Ser2 phosphorylation

Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition

Localization of RNAPII and 3′ end formation factor CstF subunits onC. elegansgenes and operons

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