Proteomics

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


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.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Schizosaccharomyces Pombe 972h-

TISSUE(S): Cell Culture

SUBMITTER: Oana Vigy  

LAB HEAD: Dominique Helmlinger

PROVIDER: PXD013256 | Pride | 2019-10-02

REPOSITORIES: Pride

Dataset's files

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Action DRS
150925_MaxQuant.andromeda.zip Other
150925_MaxQuant.txt.zip Txt
161221_MaxQuant.andromeda.zip Other
161221_MaxQuant.txt.zip Txt
170324_MaxQuant.andromeda.zip Other
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Publications

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

Elías-Villalobos Alberto A   Toullec Damien D   Faux Céline C   Séveno Martial M   Helmlinger Dominique D  

Nature communications 20191120 1


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 ord  ...[more]

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