Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD

Peter L. Hsu, Fan Yang, Whitney Smith-Kinnaman, Wen Yang, Jae Eun Song, Amber Mosley, Gabriele Varani

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The phosphorylation state of heptapeptide repeats within the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (PolII) controls the transcription cycle and is maintained by the competing action of kinases and phosphatases. Rtr1 was recently proposed to be the enzyme responsible for the transition of PolII into the elongation and termination phases of transcription by removing the phosphate marker on serine 5, but this attribution was questioned by the apparent lack of enzymatic activity. Here we demonstrate that Rtr1 is a phosphatase of new structure that is auto-inhibited by its own C-terminus. The enzymatic activity of the protein in vitro is functionally important in vivo as well: a single amino acid mutation that reduces activity leads to the same phenotype in vivo as deletion of the protein-coding gene from yeast. Surprisingly, Rtr1 dephosphorylates not only serine 5 on the CTD but also the newly described anti-termination tyrosine 1 marker, supporting the hypothesis that Rtr1 and its homologs promote the transition from transcription to termination.

Original languageEnglish
Pages (from-to)2970-2981
Number of pages12
JournalJournal of Molecular Biology
Volume426
Issue number16
DOIs
StatePublished - Aug 12 2014

Fingerprint

Dual-Specificity Phosphatases
RNA Polymerase III
RNA Polymerase II
Phosphoric Monoester Hydrolases
Serine
Tyrosine
Proteins
Phosphotransferases
Yeasts
Phosphates
Phosphorylation
Phenotype
Amino Acids
Mutation
Enzymes

Keywords

  • phosphatase
  • phosphorylation
  • RNA PolII CTD
  • RNA polymerase II
  • transcription

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD. / Hsu, Peter L.; Yang, Fan; Smith-Kinnaman, Whitney; Yang, Wen; Song, Jae Eun; Mosley, Amber; Varani, Gabriele.

In: Journal of Molecular Biology, Vol. 426, No. 16, 12.08.2014, p. 2970-2981.

Research output: Contribution to journalArticle

Hsu, Peter L. ; Yang, Fan ; Smith-Kinnaman, Whitney ; Yang, Wen ; Song, Jae Eun ; Mosley, Amber ; Varani, Gabriele. / Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD. In: Journal of Molecular Biology. 2014 ; Vol. 426, No. 16. pp. 2970-2981.
@article{581d04eef2e94cf8857e3fbceef1bb05,
title = "Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD",
abstract = "The phosphorylation state of heptapeptide repeats within the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (PolII) controls the transcription cycle and is maintained by the competing action of kinases and phosphatases. Rtr1 was recently proposed to be the enzyme responsible for the transition of PolII into the elongation and termination phases of transcription by removing the phosphate marker on serine 5, but this attribution was questioned by the apparent lack of enzymatic activity. Here we demonstrate that Rtr1 is a phosphatase of new structure that is auto-inhibited by its own C-terminus. The enzymatic activity of the protein in vitro is functionally important in vivo as well: a single amino acid mutation that reduces activity leads to the same phenotype in vivo as deletion of the protein-coding gene from yeast. Surprisingly, Rtr1 dephosphorylates not only serine 5 on the CTD but also the newly described anti-termination tyrosine 1 marker, supporting the hypothesis that Rtr1 and its homologs promote the transition from transcription to termination.",
keywords = "phosphatase, phosphorylation, RNA PolII CTD, RNA polymerase II, transcription",
author = "Hsu, {Peter L.} and Fan Yang and Whitney Smith-Kinnaman and Wen Yang and Song, {Jae Eun} and Amber Mosley and Gabriele Varani",
year = "2014",
month = "8",
day = "12",
doi = "10.1016/j.jmb.2014.06.010",
language = "English",
volume = "426",
pages = "2970--2981",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "16",

}

TY - JOUR

T1 - Rtr1 is a dual specificity phosphatase that dephosphorylates Tyr1 and Ser5 on the RNA polymerase II CTD

AU - Hsu, Peter L.

AU - Yang, Fan

AU - Smith-Kinnaman, Whitney

AU - Yang, Wen

AU - Song, Jae Eun

AU - Mosley, Amber

AU - Varani, Gabriele

PY - 2014/8/12

Y1 - 2014/8/12

N2 - The phosphorylation state of heptapeptide repeats within the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (PolII) controls the transcription cycle and is maintained by the competing action of kinases and phosphatases. Rtr1 was recently proposed to be the enzyme responsible for the transition of PolII into the elongation and termination phases of transcription by removing the phosphate marker on serine 5, but this attribution was questioned by the apparent lack of enzymatic activity. Here we demonstrate that Rtr1 is a phosphatase of new structure that is auto-inhibited by its own C-terminus. The enzymatic activity of the protein in vitro is functionally important in vivo as well: a single amino acid mutation that reduces activity leads to the same phenotype in vivo as deletion of the protein-coding gene from yeast. Surprisingly, Rtr1 dephosphorylates not only serine 5 on the CTD but also the newly described anti-termination tyrosine 1 marker, supporting the hypothesis that Rtr1 and its homologs promote the transition from transcription to termination.

AB - The phosphorylation state of heptapeptide repeats within the C-terminal domain (CTD) of the largest subunit of RNA polymerase II (PolII) controls the transcription cycle and is maintained by the competing action of kinases and phosphatases. Rtr1 was recently proposed to be the enzyme responsible for the transition of PolII into the elongation and termination phases of transcription by removing the phosphate marker on serine 5, but this attribution was questioned by the apparent lack of enzymatic activity. Here we demonstrate that Rtr1 is a phosphatase of new structure that is auto-inhibited by its own C-terminus. The enzymatic activity of the protein in vitro is functionally important in vivo as well: a single amino acid mutation that reduces activity leads to the same phenotype in vivo as deletion of the protein-coding gene from yeast. Surprisingly, Rtr1 dephosphorylates not only serine 5 on the CTD but also the newly described anti-termination tyrosine 1 marker, supporting the hypothesis that Rtr1 and its homologs promote the transition from transcription to termination.

KW - phosphatase

KW - phosphorylation

KW - RNA PolII CTD

KW - RNA polymerase II

KW - transcription

UR - http://www.scopus.com/inward/record.url?scp=84904758006&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84904758006&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2014.06.010

DO - 10.1016/j.jmb.2014.06.010

M3 - Article

C2 - 24951832

AN - SCOPUS:84904758006

VL - 426

SP - 2970

EP - 2981

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 16

ER -