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A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE151517 | GEO | 2020/11/12

REPOSITORIES: GEO

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A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming.

Project description:MicroRNAs (miRNAs) act in concert with Argonaute (AGO) proteins to repress target messenger RNAs. After AGO loading, miRNAs generally exhibit slow turnover. An important exception occurs when miRNAs encounter highly complementary targets, which can trigger a process called target-directed miRNA degradation (TDMD). During TDMD, miRNAs undergo tailing and trimming, suggesting that this is an important step in the decay mechanism. We identified a cullin-RING ubiquitin ligase (CRL), containing the substrate adaptor ZSWIM8, that mediates TDMD. The ZSWIM8 CRL interacts with AGO proteins, promotes TDMD in a tailing and trimming-independent manner, and regulates miRNA expression in multiple cell types. These findings suggest a model in which the ZSWIM8 ubiquitin ligase mediates TDMD by directing proteasomal decay of miRNA-containing complexes engaged with highly complementary targets.

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A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [TDMD]

Project description:MicroRNAs (miRNAs) act in concert with Argonaute (AGO) proteins to broadly repress mRNA targets. After AGO loading, miRNAs generally exhibit slow turnover. An important exception occurs when miRNAs encounter targets with extensive complementarity, which can trigger a process termed target-directed microRNA degradation (TDMD). Prevailing models of TDMD invoke miRNA tailing and trimming as an essential step in the decay mechanism. Here, a genome-wide screen revealed a novel cullin-RING ubiquitin ligase, which we named the DECAY complex, that mediates TDMD. The DECAY complex interacts with AGO proteins, mediates TDMD induced by multiple transcripts, and does not require tailing and trimming to elicit miRNA turnover. Based upon these findings, we propose a model in which the DECAY complex mediates TDMD by promoting proteasomal decay of miRNA-containing complexes.

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A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [miRNA-seq]

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A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [small RNA-seq]

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A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming

Project description:A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming

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Project description:A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [TDMD]

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Project description:A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [miRNA-seq]

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Project description:A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming [small RNA-seq]

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The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation.

Project description:MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to direct widespread posttranscriptional gene repression. Although association with AGO typically protects miRNAs from nucleases, extensive pairing to some unusual target RNAs can trigger miRNA degradation. We found that this target-directed miRNA degradation (TDMD) required the ZSWIM8 Cullin-RING E3 ubiquitin ligase. This and other findings support 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.

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The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-22 | GSE160304 | GEO