A Ribosome-Bound Quality Control Complex Triggers Degradation of Nascent Peptides and Signals Translation Stress | Zendy

Onn Brandman | Zendy; Jacob Stewart-Ornstein | Zendy; Daisy Y.L. Wong | Zendy; Adam G. Larson | Zendy; Christopher C. Williams | Zendy; GeneWei Li | Zendy; Sharleen Zhou | Zendy; David King | Zendy; Peter Shen | Zendy; Jimena Weibezahn | Zendy; Joshua G. Dunn | Zendy; Silvi Rouskin | Zendy; Toshifumi Inada | Zendy; Adam Frost | Zendy; Jonathan S. Weissman | Zendy

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A Ribosome-Bound Quality Control Complex Triggers Degradation of Nascent Peptides and Signals Translation Stress

Author(s) -

Onn Brandman,

Jacob Stewart-Ornstein,

Daisy Y.L. Wong,

Adam G. Larson,

Christopher C. Williams,

GeneWei Li,

Sharleen Zhou,

David King,

Peter Shen,

Jimena Weibezahn,

Joshua G. Dunn,

Silvi Rouskin,

Toshifumi Inada,

Adam Frost,

Jonathan S. Weissman

Publication year - 2012

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2012.10.044

Subject(s) - biology , translation (biology) , ribosome , degradation (telecommunications) , microbiology and biotechnology , quality (philosophy) , stress (linguistics) , computational biology , biochemistry , rna , messenger rna , computer science , gene , telecommunications , philosophy , linguistics , epistemology

The conserved transcriptional regulator heat shock factor 1 (Hsf1) is a key sensor of proteotoxic and other stress in the eukaryotic cytosol. We surveyed Hsf1 activity in a genome-wide loss-of-function library in Saccaromyces cerevisiae as well as ~78,000 double mutants and found Hsf1 activity to be modulated by highly diverse stresses. These included disruption of a ribosome-bound complex we named the Ribosome Quality Control Complex (RQC) comprising the Ltn1 E3 ubiquitin ligase, two highly conserved but poorly characterized proteins (Tae2 and Rqc1), and Cdc48 and its cofactors. Electron microscopy and biochemical analyses revealed that the RQC forms a stable complex with 60S ribosomal subunits containing stalled polypeptides and triggers their degradation. A negative feedback loop regulates the RQC, and Hsf1 senses an RQC-mediated translation-stress signal distinctly from other stresses. Our work reveals the range of stresses Hsf1 monitors and elucidates a conserved cotranslational protein quality control mechanism.

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