Phosphatase Family RTR1
Phosphatase Classification: Fold RTR1: Superfamily RTR1
RTR1 is a phosphatase conserved in eukaryotes that regulates the phosphorylation states of C-terminal domain (CTD) of RNA polymerase II.
Evolution
RTR1 is found in most eukaryotes. It is absent from the sponge genome, though it is perhaps due to the quality of genome assembly. It is single copy in human, sea urchin, fruit fly, C elegans. However, two copies are found in yeast (RTR1, RTR2).
Domain Structure
RTR1 has a conserved phosphatase domain with a unique mechanism of action [1]. Yeast RTR1 has a C-terminal region (CTR) that auto-inhibits the catalytic domain [2]. The human homolog, RPAP2, has a longer tail with limited sequence similarity to CTR, and is known to bind RNA pol II subunit Rpb6 and to be involved in pre-mRNA 3'-end formation [3].
Function
Yeast RTR1 dephosphorylates serine-5 of CTD repeats of RNA pol II [4, 5]. These findings were challenged by later studies [6], but more recent study supports its activity towards serine-5 [2] and also the anti-termination tyrosine-1 on CTD repeats [2].
References
- Irani S, Yogesha SD, Mayfield J, Zhang M, Zhang Y, Matthews WL, Nie G, Prescott NA, and Zhang YJ. Structure of Saccharomyces cerevisiae Rtr1 reveals an active site for an atypical phosphatase. Sci Signal. 2016 Mar 1;9(417):ra24. DOI:10.1126/scisignal.aad4805 |
- Hsu PL, Yang F, Smith-Kinnaman W, Yang W, Song JE, Mosley AL, and Varani G. Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD. J Mol Biol. 2014 Aug 12;426(16):2970-81. DOI:10.1016/j.jmb.2014.06.010 |
- pmid= 25639305
- Mosley AL, Pattenden SG, Carey M, Venkatesh S, Gilmore JM, Florens L, Workman JL, and Washburn MP. Rtr1 is a CTD phosphatase that regulates RNA polymerase II during the transition from serine 5 to serine 2 phosphorylation. Mol Cell. 2009 Apr 24;34(2):168-78. DOI:10.1016/j.molcel.2009.02.025 |
- Xiang K, Manley JL, and Tong L. The yeast regulator of transcription protein Rtr1 lacks an active site and phosphatase activity. Nat Commun. 2012 Jul 10;3:946. DOI:10.1038/ncomms1947 |
- Kim M, Suh H, Cho EJ, and Buratowski S. Phosphorylation of the yeast Rpb1 C-terminal domain at serines 2, 5, and 7. J Biol Chem. 2009 Sep 25;284(39):26421-6. DOI:10.1074/jbc.M109.028993 |
