TY - JOUR
T1 - A ubiquitin ligase mediates target-directed microRNA decay independently of tailing and trimming
AU - Han, Jaeil
AU - Lavigne, Collette A.
AU - Jones, Benjamin T.
AU - Zhang, He
AU - Gillett, Frank
AU - Mendell, Joshua T.
N1 - Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.
PY - 2020/12/18
Y1 - 2020/12/18
N2 - 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.
AB - 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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U2 - 10.1126/science.abc9546
DO - 10.1126/science.abc9546
M3 - Article
C2 - 33184234
AN - SCOPUS:85098742243
SN - 0036-8075
VL - 370
JO - Science
JF - Science
IS - 6523
M1 - eabc9546
ER -