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

Jaeil Han, Collette A. Lavigne, Benjamin T. Jones, He Zhang, Frank Gillett, Joshua T. Mendell

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbereabc9546
JournalScience
Volume370
Issue number6523
DOIs
StatePublished - Dec 18 2020

ASJC Scopus subject areas

  • General

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