Abstract:
: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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Matsuo Y,Tesina P,Nakajima S,Mizuno M,Endo A,Buschauer R,Cheng J,Shounai O,Ikeuchi K,Saeki Y,Becker T,Beckmann R,Inada Tdoi
10.1038/s41594-020-0393-9subject
Has Abstractpub_date
2020-04-01 00:00:00pages
323-332issue
4eissn
1545-9993issn
1545-9985pii
10.1038/s41594-020-0393-9journal_volume
27pub_type
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