Regulation of transcription elongation in response to osmostress

PLoS Genet. 2017 Nov 20;13(11):e1007090. doi: 10.1371/journal.pgen.1007090. eCollection 2017 Nov.

Abstract

Cells trigger massive changes in gene expression upon environmental fluctuations. The Hog1 stress-activated protein kinase (SAPK) is an important regulator of the transcriptional activation program that maximizes cell fitness when yeast cells are exposed to osmostress. Besides being associated with transcription factors bound at target promoters to stimulate transcriptional initiation, activated Hog1 behaves as a transcriptional elongation factor that is selective for stress-responsive genes. Here, we provide insights into how this signaling kinase functions in transcription elongation. Hog1 phosphorylates the Spt4 elongation factor at Thr42 and Ser43 and such phosphorylations are essential for the overall transcriptional response upon osmostress. The phosphorylation of Spt4 by Hog1 regulates RNA polymerase II processivity at stress-responsive genes, which is critical for cell survival under high osmostress conditions. Thus, the direct regulation of Spt4 upon environmental insults serves to stimulate RNA Pol II elongation efficiency.

MeSH terms

  • Gene Expression Regulation, Fungal / genetics*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Osmotic Pressure*
  • Protein Binding
  • RNA Polymerase II / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism
  • Serine / genetics
  • Serine / metabolism
  • Threonine / genetics
  • Threonine / metabolism
  • Transcription, Genetic / genetics*
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism

Substances

  • Nuclear Proteins
  • SPT4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • Threonine
  • Serine
  • HOG1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases
  • RNA Polymerase II

Grant support

AS was a recipient of an EMBO Long-Term Fellowship (EMBO ALTF 1394-2012). This work was supported by grants from the Spanish Ministry of Economy and Competitiveness (BFU2015-64437-P and FEDER, BFU2014-52125-REDT, BFU2014-51672-REDC to FP; BFU2014-52333-P and FEDER to EdN; BFU2016-77728-C3-1-P and BFU2013-48643-C3-1-P to SC), the Junta de Andalucía (P12-BIO1938MO to SC) and the Catalan Government (2014 SGR 599 to FP and EdN). This project was also supported by Fundación Botín, by Banco Santander through its Santander Universities Global Division to FP. FP is recipient of an ICREA Acadèmia (Generalitat de Catalunya). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.