ZNF598 Is a Quality Control Sensor of Collided Ribosomes
| Autor: | Venki Ramakrishnan, Sebastian Kraatz, Szymon Juszkiewicz, Viswanathan Chandrasekaran, Ramanujan S. Hegde, Zhewang Lin |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ubiquitin-Protein Ligases Ribosome Article 03 medical and health sciences 0302 clinical medicine Ubiquitin Humans RNA Messenger Molecular Biology Messenger RNA biology Eukaryotic Large Ribosomal Subunit Ubiquitination Cell Biology 3. Good health Cell biology Ubiquitin ligase 030104 developmental biology HEK293 Cells Protein Biosynthesis biology.protein Carrier Proteins Ribosomes 030217 neurology & neurosurgery |
| Zdroj: | Molecular Cell |
| ISSN: | 1097-4164 |
| Popis: | Summary Aberrantly slow translation elicits quality control pathways initiated by the ubiquitin ligase ZNF598. How ZNF598 discriminates physiologic from pathologic translation complexes and ubiquitinates stalled ribosomes selectively is unclear. Here, we find that the minimal unit engaged by ZNF598 is the collided di-ribosome, a molecular species that arises when a trailing ribosome encounters a slower leading ribosome. The collided di-ribosome structure reveals an extensive 40S-40S interface in which the ubiquitination targets of ZNF598 reside. The paucity of 60S interactions allows for different ribosome rotation states, explaining why ZNF598 recognition is indifferent to how the leading ribosome has stalled. The use of ribosome collisions as a proxy for stalling allows the degree of tolerable slowdown to be tuned by the initiation rate on that mRNA; hence, the threshold for triggering quality control is substrate specific. These findings illustrate how higher-order ribosome architecture can be exploited by cellular factors to monitor translation status. Graphical Abstract Highlights • ZNF598 is a direct sensor of ribosome collisions incurred by many unrelated causes • The minimal target recognized and ubiquitinated by ZNF598 is a collided di-ribosome • Collided di-ribosome structure shows that ZNF598 ubiquitin sites are near the interface • Collisions are required to terminally arrest translation in ZNF598-dependent manner Cells contain millions of ribosomes that need to translate mRNAs accurately to maintain homeostasis. Ribosomes that slow excessively during translation must be promptly resolved to avoid disease. Juszkiewicz et al. show that ribosome collisions, a sign of aberrant translation, are detected by the ubiquitin ligase ZNF598 to initiate quality control. |
| Databáze: | OpenAIRE |
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