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Status |
Public on Dec 18, 2020 |
Title |
The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation [dataset 4] |
Organism |
Caenorhabditis elegans |
Experiment type |
Non-coding RNA profiling by high throughput sequencing
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Summary |
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 the inferred role of TDMD in shaping miRNA levels in bilaterian animals.
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Overall design |
miRNA expression profiling by small-RNA sequencing of wild-type (N2) and ebax-1 (tm2321 or CZ9907) mutant C. elegans gravid adults. This study consists of libraries generated from three biological replicates.
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Web link |
https://pubmed.ncbi.nlm.nih.gov/33184237/
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Contributor(s) |
Shi CY, Bartel DP |
Citation(s) |
33184237 |
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Submission date |
Dec 16, 2020 |
Last update date |
Dec 29, 2020 |
Contact name |
Charlie Y. Shi |
E-mail(s) |
[email protected]
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Organization name |
Whitehead Institute / MIT
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Department |
Biology
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Lab |
Bartel Lab
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Street address |
455 Main St.
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City |
Cambridge |
State/province |
MA |
ZIP/Postal code |
02142 |
Country |
USA |
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Platforms (1) |
GPL18245 |
Illumina HiSeq 2500 (Caenorhabditis elegans) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE160304 |
The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation |
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Relations |
BioProject |
PRJNA685909 |
SRA |
SRP298292 |