气候变化领域集成服务门户(CCPortal): miR-122-based therapies select for three distinct resistance mechanisms based on alterations in RNA structure

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DOI	10.1073/pnas.2103671118
	miR-122-based therapies select for three distinct resistance mechanisms based on alterations in RNA structure
	Chahal J.; Gebert L.F.R.; Camargo C.; MacRae I.J.; Sagan S.M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:33
英文摘要	Hepatitis C virus (HCV) is a positive-sense RNA virus that interacts with a liver-specific microRNA called miR-122. miR-122 binds to two sites in the 5′ untranslated region of the viral genome and promotes HCV RNA accumulation. This interaction is important for viral RNA accumulation in cell culture, and miR-122 inhibitors have been shown to be effective at reducing viral titers in chronic HCV-infected patients. Herein, we analyzed resistance-associated variants that were isolated in cell culture or from patients who underwent miR-122 inhibitor-based therapy and discovered three distinct resistance mechanisms all based on changes to the structure of the viral RNA. Specifically, resistance-associated variants promoted riboswitch activity, genome stability, or positive-strand viral RNA synthesis, all in the absence of miR-122. Taken together, these findings provide insight into the mechanism(s) of miR-122-mediated viral RNA accumulation and provide mechanisms of antiviral resistance mediated by changes in RNA structure. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Hepatitis C virus; Internal ribosomal entry site; MiR-122; Resistance-associated variants; Riboswitch
语种	英语
scopus关键词	microRNA 122; virus RNA; 5' untranslated region; antiviral resistance; Article; base pairing; binding affinity; controlled study; dissociation constant; gene therapy; genomic instability; Hepatitis C virus; nonhuman; prediction; riboswitch; RNA binding; RNA conformation; RNA stability; RNA structure; RNA synthesis; virus genome
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/238827
作者单位	Department of Microbiology and Immunology, McGill University, Montréal, QC H3G 1Y6, Canada; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, San Diego, CA 92037, United States; Department of Biochemistry, McGill University, Montréal, QC H3G 1Y6, Canada
推荐引用方式 GB/T 7714	Chahal J.,Gebert L.F.R.,Camargo C.,et al. miR-122-based therapies select for three distinct resistance mechanisms based on alterations in RNA structure[J],2021,118(33).
APA	Chahal J.,Gebert L.F.R.,Camargo C.,MacRae I.J.,&Sagan S.M..(2021).miR-122-based therapies select for three distinct resistance mechanisms based on alterations in RNA structure.Proceedings of the National Academy of Sciences of the United States of America,118(33).
MLA	Chahal J.,et al."miR-122-based therapies select for three distinct resistance mechanisms based on alterations in RNA structure".Proceedings of the National Academy of Sciences of the United States of America 118.33(2021).