MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and   virus production

doi:10.1073/pnas.1408037111

CORC > 北京大学 > 工学院

	MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus production
	Chen, Antony K. ; Sengupta, Prabuddha ; Waki, Kayoko ; Van Engelenburg, Schuyler B. ; Ochiya, Takahiro ; Ablan, Sherimay D. ; Freed, Eric O. ; Lippincott-Schwartz, Jennifer
刊名	proceedings of the national academy of sciences of the united states of america
	2014
关键词	RNA CELLS BIOGENESIS RETROVIRUS TYPE-1 RECOGNITION MICROSCOPY PARTICLES ELEMENT PLASMA
DOI	10.1073/pnas.1408037111
英文摘要	MicroRNAs (miRNAs) are small, 18-22 nt long, noncoding RNAs that act as potent negative gene regulators in a variety of physiological and pathological processes. To repress gene expression, miRNAs are packaged into RNA-induced silencing complexes (RISCs) that target mRNAs for degradation and/or translational repression in a sequence-specific manner. Recently, miRNAs have been shown to also interact with proteins outside RISCs, impacting cellular processes through mechanisms not involving gene silencing. Here, we define a previously unappreciated activity of miRNAs in inhibiting RNA-protein interactions that in the context of HIV-1 biology blocks HIV virus budding and reduces virus infectivity. This occurs by miRNA binding to the nucleocapsid domain of the Gag protein, the main structural component of HIV-1 virions. The resulting miRNA-Gag complexes interfere with viral-RNA-mediated Gag assembly and viral budding at the plasma membrane, with imperfectly assembled Gag complexes endocytosed and delivered to lysosomes. The blockade of virus production by miRNA is reversed by adding the miRNA's target mRNA and stimulated by depleting Argonaute-2, suggesting that when miRNAs are not mediating gene silencing, they can block HIV-1 production through disruption of Gag assembly on membranes. Overall, our findings have significant implications for understanding how cells modulate HIV-1 infection by miRNA expression and raise the possibility that miRNAs can function to disrupt RNA-mediated protein assembly processes in other cellular contexts.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000338118900010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Multidisciplinary Sciences; SCI(E); PubMed; 17; ARTICLE; lippincj@mail.nih.gov; 26; E2676-E2683; 111
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/153820]
专题	工学院
推荐引用方式 GB/T 7714	Chen, Antony K.,Sengupta, Prabuddha,Waki, Kayoko,et al. MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus production[J]. proceedings of the national academy of sciences of the united states of america,2014.
APA	Chen, Antony K..,Sengupta, Prabuddha.,Waki, Kayoko.,Van Engelenburg, Schuyler B..,Ochiya, Takahiro.,...&Lippincott-Schwartz, Jennifer.(2014).MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus production.proceedings of the national academy of sciences of the united states of america.
MLA	Chen, Antony K.,et al."MicroRNA binding to the HIV-1 Gag protein inhibits Gag assembly and virus production".proceedings of the national academy of sciences of the united states of america (2014).