Chaperone-mediated ordered assembly of the SAGA and NuA4 transcription co-activator complexes in yeast

Nat Commun. 2019 Nov 20;10(1):5237. doi: 10.1038/s41467-019-13243-w.

Abstract

Transcription initiation involves the coordinated activities of large multimeric complexes, but little is known about their biogenesis. Here we report several principles underlying the assembly and topological organization of the highly conserved SAGA and NuA4 co-activator complexes, which share the Tra1 subunit. We show that Tra1 contributes to the overall integrity of NuA4, whereas, within SAGA, it specifically controls the incorporation of the de-ubiquitination module (DUB), as part of an ordered assembly pathway. Biochemical and functional analyses reveal the mechanism by which Tra1 specifically interacts with either SAGA or NuA4. Finally, we demonstrate that Hsp90 and its cochaperone TTT promote Tra1 de novo incorporation into both complexes, indicating that Tra1, the sole pseudokinase of the PIKK family, shares a dedicated chaperone machinery with its cognate kinases. Overall, our work brings mechanistic insights into the assembly of transcriptional complexes and reveals the contribution of dedicated chaperones to this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation, Fungal
  • HSP90 Heat-Shock Proteins / metabolism*
  • Histone Acetyltransferases / metabolism*
  • Molecular Chaperones
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Trans-Activators / metabolism*
  • Transcription, Genetic

Substances

  • HSP82 protein, S cerevisiae
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • SAGA complex, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • TRA1 protein, S cerevisiae
  • Trans-Activators
  • Histone Acetyltransferases
  • NuA4 protein, S cerevisiae