Pervasive, Coordinated Protein-Level Changes Driven by Transcript Isoform Switching during Meiosis

Cell. 2018 Feb 22;172(5):910-923.e16. doi: 10.1016/j.cell.2018.01.035.


To better understand the gene regulatory mechanisms that program developmental processes, we carried out simultaneous genome-wide measurements of mRNA, translation, and protein through meiotic differentiation in budding yeast. Surprisingly, we observed that the levels of several hundred mRNAs are anti-correlated with their corresponding protein products. We show that rather than arising from canonical forms of gene regulatory control, the regulation of at least 380 such cases, or over 8% of all measured genes, involves temporally regulated switching between production of a canonical, translatable transcript and a 5' extended isoform that is not efficiently translated into protein. By this pervasive mechanism for the modulation of protein levels through a natural developmental program, a single transcription factor can coordinately activate and repress protein synthesis for distinct sets of genes. The distinction is not based on whether or not an mRNA is induced but rather on the type of transcript produced.

Keywords: LUTI; coordination; differentiation; gene expression; isoform; meiosis; ribosome profiling; transcription factor; translation; uORF.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Meiosis / genetics*
  • Models, Biological
  • Molecular Sequence Annotation
  • Protein Biosynthesis
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proteome / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription Factors / metabolism


  • Protein Isoforms
  • Proteome
  • RNA, Messenger
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors