Origin of translational control by eIF2α phosphorylation: insights from genome-wide translational profiling studies in fission yeast

Curr Genet. 2021 Jun;67(3):359-368. doi: 10.1007/s00294-020-01149-w. Epub 2021 Jan 9.

Abstract

During amino acid limitation, the protein kinase Gcn2 phosphorylates the α subunit of eIF2, thereby regulating mRNA translation. In yeast Saccharomyces cerevisiae and mammals, eIF2α phosphorylation regulates translation of related transcription factors Gcn4 and Atf4 through upstream open reading frames (uORFs) to activate transcription genome wide. However, mammals encode three more eIF2α kinases activated by distinct stimuli. Did the translational control system involving eIF2α phosphorylation evolve from so simple (as found in yeast S. cerevisiae) to complex (as found in humans)? Recent genome-wide translational profiling studies of amino acid starvation response in the fission yeast Schizosaccharomyces pombe provide an unexpected answer to this question.

Keywords: Evolution; Schizosaccharomyces pombe; Translational control; eIF2α kinase; uORF.

Publication types

  • Review

MeSH terms

  • Activating Transcription Factor 4 / genetics*
  • Amino Acids / genetics
  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Eukaryotic Initiation Factor-2 / genetics*
  • Gene Expression Regulation, Fungal
  • Humans
  • Open Reading Frames / genetics
  • Phosphorylation
  • Protein Biosynthesis*
  • RNA, Messenger / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics*

Substances

  • Amino Acids
  • Basic-Leucine Zipper Transcription Factors
  • Eukaryotic Initiation Factor-2
  • GCN4 protein, S cerevisiae
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Activating Transcription Factor 4