气候变化领域集成服务门户(CCPortal): Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity

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DOI	10.1073/pnas.2021719118
	Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity
	Jayabalan A.K.; Adivarahan S.; Koppula A.; Abraham R.; Batish M.; Zenklusen D.; Griffin D.E.; Leung A.K.L.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	While biomolecular condensates have emerged as an important biological phenomenon, mechanisms regulating their composition and the ways that viruses hijack these mechanisms remain unclear. The mosquito-borne alphaviruses cause a range of diseases from rashes and arthritis to encephalitis, and no licensed drugs are available for treatment or vaccines for prevention. The alphavirus virulence factor nonstructural protein 3 (nsP3) suppresses the formation of stress granules (SGs)-a class of cytoplasmic condensates enriched with translation initiation factors and formed during the early stage of infection. nsP3 has a conserved N-terminal macrodomain that hydrolyzes ADP-ribose from ADP-ribosylated proteins and a C-terminal hypervariable domain that binds the essential SG component G3BP1. Here, we show that macrodomain hydrolase activity reduces the ADP-ribosylation of G3BP1, disassembles virus-induced SGs, and suppresses SG formation. Expression of nsP3 results in the formation of a distinct class of condensates that lack translation initiation factors but contain G3BP1 and other SG-associated RNA-binding proteins. Expression of ADP-ribosylhydrolase-deficient nsP3 results in condensates that retain translation initiation factors as well as RNA-binding proteins, similar to SGs. Therefore, our data reveal that ADP-ribosylation controls the composition of biomolecular condensates, specifically the localization of translation initiation factors, during alphavirus infection. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	ADP-ribosylation; Alphavirus; Biomolecular condensates; Macrodomain; Stress granules
语种	英语
scopus关键词	adenosine diphosphate; adenosine diphosphate ribosylhydrolase; hydrolase; RNA binding protein; unclassified drug; adenosine diphosphate ribosylation; Alphavirus; Alphavirus infection; amino terminal sequence; Article; carboxy terminal sequence; controlled study; cytoplasm; nonhuman; priority journal; protein expression; translation initiation; virus virulence; wild type
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/180738
作者单位	Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States; Départment de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC H3T 1J4, Canada; Department of Biological Sciences, University of Delaware, Newark, DE 19716, United States; W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, United States; Department of Medical and Molecular Sciences, University of Delaware, Newark, DE 19716, United States; Department of Molecular Biology and Genetics, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, United States; Department of Oncology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, United States
推荐引用方式 GB/T 7714	Jayabalan A.K.,Adivarahan S.,Koppula A.,et al. Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity[J],2021,118(6).
APA	Jayabalan A.K..,Adivarahan S..,Koppula A..,Abraham R..,Batish M..,...&Leung A.K.L..(2021).Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Jayabalan A.K.,et al."Stress granule formation, disassembly, and composition are regulated by alphavirus ADP-ribosylhydrolase activity".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).