气候变化领域集成服务门户(CCPortal): The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation

CCPortal

DOI	10.1126/science.abc9359
	The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation
	Shi C.Y.; Kingston E.R.; Kleaveland B.; Lin D.H.; Stubna M.W.; Bartel D.P.
发表日期	2020
ISSN	0036-8075
卷号	370 期号:6523
英文摘要	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 targetdirected 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. © 2020 American Association for the Advancement of Science. All rights reserved.
英文关键词	long untranslated RNA; long untranslated RNA CYRANO; microRNA; microRNA 7; nuclease; proteasome; ubiquitin protein ligase; ubiquitin protein ligase ZSWIM8; unclassified drug; argonaute protein; Caenorhabditis elegans protein; Drosophila protein; EBAX-1 protein, C elegans; elongin; long noncoding RNA OIP5, human; long untranslated RNA; microRNA; Mir7 microRNA, Drosophila; MIRN7 microRNA, human; MIRN7 microRNA, mouse; ubiquitin protein ligase; ZSWIM8 protein, human; Zswim8 protein, mouse; animal; cell; enzyme activity; experimental study; gene expression; genetic engineering; physiological response; protein; 3' untranslated region; Article; clustered regularly interspaced short palindromic repeat; conformational transition; Drosophila; enzyme activity; gene knockdown; genetic stability; nematode; nonhuman; priority journal; RNA degradation; target directed miRNA degradation; ubiquitination; virus replication; animal; Caenorhabditis elegans; genetics; human; K-562 cell line; metabolism; mouse; NIH 3T3 cell line; protein degradation; RNA stability; Mammalia; Nematoda; Animals; Argonaute Proteins; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Drosophila; Drosophila Proteins; Elongin; Gene Knockdown Techniques; Humans; K562 Cells; Mice; MicroRNAs; NIH 3T3 Cells; Proteolysis; RNA Stability; RNA, Long Noncoding; Ubiquitin-Protein Ligases
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/245462
作者单位	Whitehead Institute for Biomedical Research, Howard Hughes Medical Institute, Cambridge, MA 02142, United States; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, United States; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, United States; Department of Pathology and Lab Medicine, Weill Cornell Medicine, New York, NY 10065, United States
推荐引用方式 GB/T 7714	Shi C.Y.,Kingston E.R.,Kleaveland B.,et al. The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation[J],2020,370(6523).
APA	Shi C.Y.,Kingston E.R.,Kleaveland B.,Lin D.H.,Stubna M.W.,&Bartel D.P..(2020).The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation.Science,370(6523).
MLA	Shi C.Y.,et al."The ZSWIM8 ubiquitin ligase mediates target-directed microRNA degradation".Science 370.6523(2020).