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

被引：152

作者：

Han, Jaeil ^{[1
]}

LaVigne, Collette A. ^{[1
]}

Jones, Benjamin T. ^{[1
]}

Zhang, He ^{[2
,3
]}

Gillett, Frank ^{[1
]}

Mendell, Joshua T. ^{[4
,5
,6
]}

机构：

[1] Univ Texas Southwestern Med Ctr Dallas, Dept Mol Biol, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr Dallas, Quantitat Biomed Res Ctr, Dallas, TX 75390 USA

[3] Univ Texas Southwestern Med Ctr Dallas, Dept Populat & Data Sci, Dallas, TX 75390 USA

[4] Univ Texas Southwestern Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Hamon Ctr Regenerat Sci & Med, Dallas, TX 75390 USA

[6] Univ Texas Southwestern Med Ctr Dallas, Howard Hughes Med Inst, Dallas, TX 75390 USA

来源：

SCIENCE | 2020年 / 370卷 / 6523期

关键词：

RNA; DEGRADATION; IDENTIFICATION; EXPRESSION; BINDING; FAMILY;

D O I：

10.1126/science.abc9546

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1432 / +

页数：11

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