Not5-dependent co-translational assembly of Ada2 and Spt20 is essential for functional integrity of SAGA

Nucleic Acids Res. 2017 Feb 17;45(3):1186-1199. doi: 10.1093/nar/gkw1059.

Abstract

Acetylation of histones regulates gene expression in eukaryotes. In the yeast Saccharomyces cerevisiae it depends mainly upon the ADA and SAGA histone acetyltransferase complexes for which Gcn5 is the catalytic subunit. Previous screens have determined that global acetylation is reduced in cells lacking subunits of the Ccr4–Not complex, a global regulator of eukaryotic gene expression. In this study we have characterized the functional connection between the Ccr4–Not complex and SAGA. We show that SAGA mRNAs encoding a core set of SAGA subunits are tethered together for co-translational assembly of the encoded proteins. Ccr4–Not subunits bind SAGA mRNAs and promote the co-translational assembly of these subunits. This is needed for integrity of SAGA. In addition, we determine that a glycolytic enzyme, the glyceraldehyde-3-phosphate dehydrogenase Tdh3, a prototypical moonlighting protein, is tethered at this site of Ccr4–Not-dependent co-translational SAGA assembly and functions as a chaperone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / chemistry
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / genetics
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / metabolism
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / genetics
  • Histone Acetyltransferases / metabolism
  • Models, Biological
  • Mutation
  • Protein Multimerization / genetics
  • Protein Subunits
  • RNA, Fungal / genetics
  • RNA, Fungal / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribonucleases / chemistry
  • Ribonucleases / genetics
  • Ribonucleases / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Trans-Activators / chemistry
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • ADA2 protein, S cerevisiae
  • NOT5 protein, S cerevisiae
  • Protein Subunits
  • RNA, Fungal
  • RNA, Messenger
  • SAGA complex, S cerevisiae
  • SPT20 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)
  • TDH3 protein, S cerevisiae
  • GCN5 protein, S cerevisiae
  • Histone Acetyltransferases
  • CCR4 protein, S cerevisiae
  • Ribonucleases