Difference between revisions of "CTD Phosphorylation"
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Revision as of 23:01, 14 May 2016
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. |
? | 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
- 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 |
- 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 |
- 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 |
- 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 |
- 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 |
- Yang XJ. Multisite protein modification and intramolecular signaling. Oncogene. 2005 Mar 3;24(10):1653-62. DOI:10.1038/sj.onc.1208173 |
- 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 |
- 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 |
- 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 |