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| Status |
Public on Dec 18, 2020 |
| Title |
The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation [dataset 1] |
| Organism |
Homo sapiens |
| Experiment type |
Non-coding RNA profiling by high throughput sequencing
|
| 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 K562 cells expressing inducible KRAB-dCas9 and either a control guide RNA (gRNA), a gRNA targeting CYRANO, or one of two gRNAs targeting ZSWIM8. This study consists of 12 libraries generated from three biological replicates per gRNA.
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| Contributor(s) |
Shi CY, Bartel DP |
| Citation(s) |
33184237 |
| |
| Submission date |
Dec 16, 2020 |
| Last update date |
Jan 06, 2021 |
| Contact name |
Charlie Y. Shi |
| E-mail(s) |
shic@mit.edu
|
| Organization name |
Whitehead Institute / MIT
|
| Department |
Biology
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| Lab |
Bartel Lab
|
| Street address |
455 Main St.
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE160304 |
The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation |
|
| Relations |
| BioProject |
PRJNA685904 |
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