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

Alberto Elías-Villalobos, Damien Toullec, Céline Faux, Martial Séveno, View ORCID ProfileDominique Helmlinger
doi: https://doi.org/10.1101/524959
Alberto Elías-Villalobos
1CRBM, CNRS, University of Montpellier, Montpellier, France
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Damien Toullec
1CRBM, CNRS, University of Montpellier, Montpellier, France
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Céline Faux
1CRBM, CNRS, University of Montpellier, Montpellier, France
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Martial Séveno
2BioCampus Montpellier, CNRS, INSERM, University of Montpellier, Montpellier, France
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Dominique Helmlinger
1CRBM, CNRS, University of Montpellier, Montpellier, France
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  • ORCID record for Dominique Helmlinger
  • For correspondence: dhelmlinger@crbm.cnrs.fr
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Abstract

Transcription initiation involves the coordinated activities of large multimeric complexes that are organized into functional modules. Little is known about the mechanisms and pathways that govern their assembly from individual components. We report here several principles governing the assembly of the highly conserved SAGA and NuA4 co-activator complexes. Using fission yeast, which contain two functionally non-redundant paralogs of the shared Tra1 subunit, we demonstrate that Tra1 contributes to scaffolding the entire NuA4 complex. In contrast, within SAGA, Tra1 specifically promotes the incorporation of the de-ubiquitination module (DUB), defining an ordered assembly pathway. Biochemical and functional analyses elucidated the mechanism by which Tra1 assemble differentially into SAGA or NuA4 and identified a small, conserved region of Spt20 that is both necessary and sufficient to anchor Tra1 within SAGA. Finally, we establish that Hsp90 and its cochaperone TTT are required for Tra1 de novo incorporation into both SAGA and NuA4, indicating that Tra1, a pseudokinase of the PIKK family, shares a dedicated chaperone machinery with its cognate kinases. Overall, our work brings mechanistic insights into the de novo assembly of transcriptional complexes through ordered pathways and reveals the contribution of dedicated chaperones to this process.

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Posted February 22, 2019.
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Chaperone-mediated ordered assembly of the SAGA and NuA4 transcription co-activator complexes
Alberto Elías-Villalobos, Damien Toullec, Céline Faux, Martial Séveno, Dominique Helmlinger
bioRxiv 524959; doi: https://doi.org/10.1101/524959
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Chaperone-mediated ordered assembly of the SAGA and NuA4 transcription co-activator complexes
Alberto Elías-Villalobos, Damien Toullec, Céline Faux, Martial Séveno, Dominique Helmlinger
bioRxiv 524959; doi: https://doi.org/10.1101/524959

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