To Degrade a MicroRNA, Destroy Its Argonaute Protein
| Autor: | Pei Hsuan Wu, Phillip D. Zamore |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Proteasome Endopeptidase Complex
Argonaute Proteins / metabolism biology Proteasome Endopeptidase Complex / metabolism Ubiquitin Ubiquitin-Protein Ligases fungi Argonaute Proteins / genetics RNA Cell Biology Argonaute Article Ubiquitin ligase Cell biology MicroRNAs MicroRNAs / genetics Proteasome Ubiquitin-Protein Ligases / metabolism Ubiquitin / metabolism microRNA Argonaute Proteins biology.protein Molecular Biology |
| Zdroj: | Science Molecular cell, Vol. 81, No 2 (2021) pp. 223-225 |
| ISSN: | 1097-4164 1097-2765 |
| Popis: | MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to direct widespread post-transcriptional gene repression. Although association with AGO typically protects miRNAs from nucleases, extensive pairing to some unusual target RNAs can trigger miRNA degradation. Here we found that this target-directed miRNA degradation (TDMD) required the ZSWIM8 Cullin-RING E3 ubiquitin ligase. This and other findings suggested and supported a mechanistic model of TDMD in which target-directed proteolysis of AGO by the ubiquitin–proteasome pathway exposes the miRNA for degradation. Moreover, loss-of-function studies indicated that the ZSWIM8 Cullin-RING ligase accelerates degradation of numerous miRNAs in cells of mammals, flies, and nematodes, thereby specifying the half-lives of most short-lived miRNAs. These results elucidate the mechanism of TDMD and expand its inferred role in shaping miRNA levels in bilaterian animals. |
| Databáze: | OpenAIRE |
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