CTD Phosphorylation

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Main Page:CTD Phosphorylation

Introduction

The C-terminal domain (CTD) of RNA polymerase II's largest subunit undergoes patterned dynamic phosphorylation during the transcription cycle. Each phosphorylation pattern recruits a particular set of mRNA-processing and histone-modifying factors. The CTD contains many copies of a heptapeptide repeat with 5 phosphorylation sites in the consensus sequence (Y1, S2, T4, S5, S7). In vivo phosphorylation occurs mainly on serine residues. This complex phosphorylation pattern is regulated by several phosphatases and kinases [1].

Phosphatases

Mammals Yeast Group Family Substrate Stage Evolution (from yeast to human) Note
FCP1 FCP1 HAD FCP pSer2, pThr4 [2] To Recycling From yeast to human
SCP SCP HAD FCP pSer5 To cleavage, polyA and termination From yeast to human The function toward pSer5 of one of its member, SCP1, has been verified in mammals, but not in yeast, yet.
SSU72 SSU72 CC2 SSU72 pSer5 To cleavage, polyA and termination From yeast to human 1) Its function toward pSer5 has been verified in yeast, but not mammals. 2) Unlike other phosphatases, it has a fold similar to LMWPTP rather than HAD.
HSPC129 N/A HAD FCP  ?  ? From Monosiga to human but lost in fly 1) In vitro activity toward CTD. 2) HSPC129 was divergent from SCP family.
UBLCP1 N/A HAD SCP  ?  ? From anemone to human but lost in nematode 1) In vitro activity toward CTD.
RPAP2 RTR1, RTR2 RTR1 RTR1 pSer5, pTyr1 RTR1 is found in most of eukaryotes. It is absent from Monosiga and sponge genome
 ? N/A  ?  ? pSer7  ?  ? Observed phosphorylated pSer7, but the phosphatase and kinase are unknown.

Kinases

Mammals Yeast Group Family Subfamily Substrate Stage Evolution Note
CDK7 KIN28 CMGC CDK CDK7 Ser5, Ser7 To initiation From yeast to human but lost in Monosiga? 1) CDK7 is a component of transcription factor TFIIH. 2) KinBase shows it is absent from Monosiga.
CDK9 Bur1 CMGC CDK CDK9 Ser2, Ser7 To elongation From yeast to human but lost in Monosiga? 1) CDK9 is the catalytic subunit of the positive transcription elongation factor (P-TEF)b complex. 2) KinBase shows it is absent from Monosiga.
CRK7 CTK1 CMGC CDK CRK7 Ser2 To elongation From Giardia to human but lost in Tetrahymena It has been verified in yeast, but not in mammals.
CDK8 CDK8 CMGC CDK CDK8 Ser2 and Ser5 In the pool of pol II? From yeast to human
CDC2 CDK1 CMGC CDK CDC2 Ser2 and Ser5 In the pool of pol II? From Giardia to human In KInbase, conserved in yeast in the tree, but absent in the hits.
ERK1/2 FUS3, KSS1, SLT2, SMK1, YKL161C CMGC MAPK ERK1 Ser5 In the pool of pol II? From Monosiga to human Many yeast proteins in this subfamily of extracellular signal-related kinase 1/2 (ERK1 in KinBase).

References

  1. Buratowski S. Progression through the RNA polymerase II CTD cycle. Mol Cell. 2009 Nov 25;36(4):541-6. DOI:10.1016/j.molcel.2009.10.019 | PubMed ID:19941815 | HubMed [Buratowski]
  2. Hsin JP, Xiang K, and Manley JL. Function and control of RNA polymerase II C-terminal domain phosphorylation in vertebrate transcription and RNA processing. Mol Cell Biol. 2014 Jul;34(13):2488-98. DOI:10.1128/MCB.00181-14 | PubMed ID:24752900 | HubMed [hsin2014]
  3. Akhtar MS, Heidemann M, Tietjen JR, Zhang DW, Chapman RD, Eick D, and Ansari AZ. TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA polymerase II. Mol Cell. 2009 May 15;34(3):387-93. DOI:10.1016/j.molcel.2009.04.016 | PubMed ID:19450536 | HubMed [Akhtar]
  4. Tietjen JR, Zhang DW, Rodríguez-Molina JB, White BE, Akhtar MS, Heidemann M, Li X, Chapman RD, Shokat K, Keles S, Eick D, and Ansari AZ. Chemical-genomic dissection of the CTD code. Nat Struct Mol Biol. 2010 Sep;17(9):1154-61. DOI:10.1038/nsmb.1900 | PubMed ID:20802488 | HubMed [Tietjen]
  5. Kim H, Erickson B, Luo W, Seward D, Graber JH, Pollock DD, Megee PC, and Bentley DL. Gene-specific RNA polymerase II phosphorylation and the CTD code. Nat Struct Mol Biol. 2010 Oct;17(10):1279-86. DOI:10.1038/nsmb.1913 | PubMed ID:20835241 | HubMed [Kim]
  6. Yang XJ. Multisite protein modification and intramolecular signaling. Oncogene. 2005 Mar 3;24(10):1653-62. DOI:10.1038/sj.onc.1208173 | PubMed ID:15744326 | HubMed [Yang]
  7. Chapman RD, Heidemann M, Hintermair C, and Eick D. Molecular evolution of the RNA polymerase II CTD. Trends Genet. 2008 Jun;24(6):289-96. DOI:10.1016/j.tig.2008.03.010 | PubMed ID:18472177 | HubMed [Chapman]
  8. Stiller JW and Hall BD. Evolution of the RNA polymerase II C-terminal domain. Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6091-6. DOI:10.1073/pnas.082646199 | PubMed ID:11972039 | HubMed [Stiller]
  9. Egloff S and Murphy S. Cracking the RNA polymerase II CTD code. Trends Genet. 2008 Jun;24(6):280-8. DOI:10.1016/j.tig.2008.03.008 | PubMed ID:18457900 | HubMed [Egloff]
All Medline abstracts: PubMed | HubMed