MPK1/SLT2 Links Multiple Stress Responses with Gene Expression in Budding Yeast by Phosphorylating Tyr1 of the RNAP II CTD

Nathan Yurko, Xiaochuan Liu, Takashi Yamazaki, Mainul Hoque, Bin Tian, James L. Manley

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The RNA polymerase II largest subunit C-terminal domain consists of repeated YSPTSPS heptapeptides. The role of tyrosine-1 (Tyr1) remains incompletely understood, as, for example, mutating all Tyr1 residues to Phe (Y1F) is lethal in vertebrates but a related mutant has only a mild phenotype in S. pombe. Here we show that Y1F substitution in budding yeast resulted in a strong slow-growth phenotype. The Y1F strain was also hypersensitive to several different cellular stresses that involve MAP kinase signaling. These phenotypes were all linked to transcriptional changes, and we also identified genetic and biochemical interactions between Tyr1 and both transcription initiation and termination factors. Further studies uncovered defects related to MAP kinase I (Slt2) pathways, and we provide evidence that Slt2 phosphorylates Tyr1 in vitro and in vivo. Our study has thus identified Slt2 as a Tyr1 kinase, and in doing so provided links between stress response activation and Tyr1 phosphorylation. The role of tyrosine-1 in the RNA polymerase II C-terminal domain is unclear. Yurko et al. find that it is phosphorylated in budding yeast by the MAP kinase Slt2, and that it is important for both transcription initiation and termination as well as responses to various cellular stresses.

Original languageEnglish (US)
Pages (from-to)913-925.e3
JournalMolecular cell
Volume68
Issue number5
DOIs
StatePublished - Dec 7 2017

Fingerprint

Saccharomycetales
Tyrosine
Gene Expression
Phosphotransferases
Phenotype
RNA Polymerase III
Peptide Initiation Factors
Schizosaccharomyces
RNA Polymerase II
Protein-Tyrosine Kinases
Vertebrates
Molecular Biology
Phosphorylation
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Keywords

  • Mediator
  • NNS complex
  • RNA polymerase II
  • Slt2 kinase
  • stress response
  • transcription termination
  • tyrosine phosphorylation

Cite this

Yurko, Nathan ; Liu, Xiaochuan ; Yamazaki, Takashi ; Hoque, Mainul ; Tian, Bin ; Manley, James L. / MPK1/SLT2 Links Multiple Stress Responses with Gene Expression in Budding Yeast by Phosphorylating Tyr1 of the RNAP II CTD. In: Molecular cell. 2017 ; Vol. 68, No. 5. pp. 913-925.e3.
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MPK1/SLT2 Links Multiple Stress Responses with Gene Expression in Budding Yeast by Phosphorylating Tyr1 of the RNAP II CTD. / Yurko, Nathan; Liu, Xiaochuan; Yamazaki, Takashi; Hoque, Mainul; Tian, Bin; Manley, James L.

In: Molecular cell, Vol. 68, No. 5, 07.12.2017, p. 913-925.e3.

Research output: Contribution to journalArticle

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