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DOI10.1073/pnas.2020454118
A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms
Zhou L.; Miller C.; Miraglia L.J.; Romero A.; Mure L.S.; Panda S.; Kay S.A.
发表日期2021
ISSN00278424
卷号118期号:1
英文摘要The regulatory mechanisms of circadian rhythms have been studied primarily at the level of the transcription-translation feedback loops of protein-coding genes. Regulatory modules involving noncoding RNAs are less thoroughly understood. In particular, emerging evidence has revealed the important role of microRNAs (miRNAs) in maintaining the robustness of the circadian system. To identify miRNAs that have the potential to modulate circadian rhythms, we conducted a genome-wide miRNA screen using U2OS luciferase reporter cells. Among 989 miRNAs in the library, 120 changed the period length in a dose-dependent manner. We further validated the circadian regulatory function of an miRNA cluster, miR-183/96/182, both in vitro and in vivo. We found that all three members of this miRNA cluster can modulate circadian rhythms. Particularly, miR-96 directly targeted a core circadian clock gene, PER2. The knockout of the miR-183/96/182 cluster in mice showed tissue-specific effects on circadian parameters and altered circadian rhythms at the behavioral level. This study identified a large number of miRNAs, including the miR-183/96/182 cluster, as circadian modulators. We provide a resource for further understanding the role of miRNAs in the circadian network and highlight the importance of miRNAs as a genome-wide layer of circadian clock regulation. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Circadian rhythms; Genome-wide screen; MiR-183/96/182 cluster; MiRNA
语种英语
scopus关键词luciferase; microRNA; microRNA 182; microRNA 183; microRNA 96; PER2 protein; unclassified drug; Article; circadian rhythm; controlled study; gene cluster; gene function; gene library; gene number; human; human cell; in vitro study; in vivo study; medical parameters; PER2 gene; priority journal; regulatory mechanism; RNA analysis; tissue specificity; U2OS cell line; validation study
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/181157
作者单位Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, United States; Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, United States; Salk Institute for Biological Studies, San Diego, CA 92037, United States
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Zhou L.,Miller C.,Miraglia L.J.,et al. A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms[J],2021,118(1).
APA Zhou L..,Miller C..,Miraglia L.J..,Romero A..,Mure L.S..,...&Kay S.A..(2021).A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms.Proceedings of the National Academy of Sciences of the United States of America,118(1).
MLA Zhou L.,et al."A genome-wide microRNA screen identifies the microRNA-183/96/182 cluster as a modulator of circadian rhythms".Proceedings of the National Academy of Sciences of the United States of America 118.1(2021).
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