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TitleRQT complex dissociates ribosomes collided on endogenous RQC substrate SDD1.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 4, Page 323-332, Year 2020
Publish dateMar 23, 2020
AuthorsYoshitaka Matsuo / Petr Tesina / Shizuka Nakajima / Masato Mizuno / Akinori Endo / Robert Buschauer / Jingdong Cheng / Okuto Shounai / Ken Ikeuchi / Yasushi Saeki / Thomas Becker / Roland Beckmann / Toshifumi Inada /
PubMed AbstractRibosome-associated quality control (RQC) represents a rescue pathway in eukaryotic cells that is triggered upon translational stalling. Collided ribosomes are recognized for subsequent dissociation ...Ribosome-associated quality control (RQC) represents a rescue pathway in eukaryotic cells that is triggered upon translational stalling. Collided ribosomes are recognized for subsequent dissociation followed by degradation of nascent peptides. However, endogenous RQC-inducing sequences and the mechanism underlying the ubiquitin-dependent ribosome dissociation remain poorly understood. Here, we identified SDD1 messenger RNA from Saccharomyces cerevisiae as an endogenous RQC substrate and reveal the mechanism of its mRNA-dependent and nascent peptide-dependent translational stalling. In vitro translation of SDD1 mRNA enabled the reconstitution of Hel2-dependent polyubiquitination of collided disomes and, preferentially, trisomes. The distinct trisome architecture, visualized using cryo-EM, provides the structural basis for the more-efficient recognition by Hel2 compared with that of disomes. Subsequently, the Slh1 helicase subunit of the RQC trigger (RQT) complex preferentially dissociates the first stalled polyubiquitinated ribosome in an ATP-dependent manner. Together, these findings provide fundamental mechanistic insights into RQC and its physiological role in maintaining cellular protein homeostasis.
External linksNat Struct Mol Biol / PubMed:32203490
MethodsEM (single particle)
Resolution2.8 - 3.3 Å
Structure data

10262

6snt

EMDB-10262, PDB-6snt:
Yeast 80S ribosome stalled on SDD1 mRNA.
Method: EM (single particle) / Resolution: 2.8 Å

10315

6sv4

EMDB-10315, PDB-6sv4:
The cryo-EM structure of SDD1-stalled collided trisome.
Method: EM (single particle) / Resolution: 3.3 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • saccharomyces cerevisiae (brewer's yeast)
  • Baker's yeast (brewer's yeast)
KeywordsTRANSLATION / 80S / stalling / SDD1 / trisome / ribosome / collision

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