The ASC-1 Complex Disassembles Collided Ribosomes
| Autor: | Szymon Juszkiewicz, Ramanujan S. Hegde, Jesper Q. Svejstrup, Shaun H. Speldewinde, Li Wan |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Amino Acid Transport System y+
translation Ribosome Article ASCC3 03 medical and health sciences 0302 clinical medicine Ubiquitin GTP-Binding Proteins Polysome Ribosome Subunits Animals Humans Eukaryotic Small Ribosomal Subunit quality control Molecular Biology RQC 030304 developmental biology 0303 health sciences Messenger RNA Cell-Free System biology DNA Helicases Ubiquitination Nuclear Proteins Helicase Cell Biology Ribosomal RNA Cell biology Ubiquitin ligase helicase HEK293 Cells ribosome Multiprotein Complexes Polyribosomes Protein Biosynthesis biology.protein Rabbits Carrier Proteins Ribosomes 030217 neurology & neurosurgery Peptide Termination Factors |
| Zdroj: | Molecular Cell |
| ISSN: | 1097-2765 |
| DOI: | 10.1016/j.molcel.2020.06.006 |
| Popis: | Summary Translating ribosomes that slow excessively incur collisions with trailing ribosomes. Persistent collisions are detected by ZNF598, a ubiquitin ligase that ubiquitinates sites on the ribosomal 40S subunit to initiate pathways of mRNA and protein quality control. The collided ribosome complex must be disassembled to initiate downstream quality control, but the mechanistic basis of disassembly is unclear. Here, we reconstitute the disassembly of a collided polysome in a mammalian cell-free system. The widely conserved ASC-1 complex (ASCC) containing the ASCC3 helicase disassembles the leading ribosome in an ATP-dependent reaction. Disassembly, but not ribosome association, requires 40S ubiquitination by ZNF598, but not GTP-dependent factors, including the Pelo-Hbs1L ribosome rescue complex. Trailing ribosomes can elongate once the roadblock has been removed and only become targets if they subsequently stall and incur collisions. These findings define the specific role of ASCC during ribosome-associated quality control and identify the molecular target of its activity. Graphical Abstract Highlights • ASC-1 Complex (ASCC) disassembles collided ribosomes ubiquitinated by ZNF598 • ATPase activity of the ASCC3 helicase is needed to split the leading stalled ribosome • ASCC generates 60S-nascent chains targeted by the ribosome quality control complex • Dispatch of the lead ribosome by ASCC allows trailing ribosomes to resume translation Ribosomes translate mRNAs at ~4 to 6 codons per second. Various mRNA defects cause a ribosome to slow, leading to collisions with trailing ribosomes. Juszkiewicz et al. show that the ASC-1 complex containing the helicase ASCC3 selectively dissociates the lead ribosome of a collision, allowing trailing ribosomes to continue translation. |
| Databáze: | OpenAIRE |
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