Global Changes in the RNA Binding Specificity of HIV-1 Gag Regulate Virion Genesis

被引：164

作者：

Kutluay, Sebla B. ^{[1
]}

Zang, Trinity ^{[1
,2
]}

Blanco-Melo, Daniel ^{[1
]}

Powell, Chelsea ^{[1
]}

Jannain, David ^{[1
]}

Errando, Manel ^{[3
]}

Bieniasz, Paul D. ^{[1
,2
]}

机构：

[1] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, Lab Retrovirol, New York, NY 10016 USA

[2] Rockefeller Univ, Aaron Diamond AIDS Res Ctr, Howard Hughes Med Inst, New York, NY 10016 USA

[3] Columbia Univ, Barnard Coll, Dept Phys & Astron, New York, NY 10027 USA

来源：

CELL | 2014年 / 159卷 / 05期

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; CIS-ACTING SEQUENCES; TYPE-1; RNA; NUCLEOCAPSID PROTEIN; MEMBRANE ASSOCIATION; SECONDARY STRUCTURE; PACKAGING SIGNAL; VIRAL PARTICLES; CELLULAR RNAS; MATRIX DOMAIN;

D O I：

10.1016/j.cell.2014.09.057

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The HIV-1 Gag protein orchestrates all steps of virion genesis, including membrane targeting and RNA recruitment into virions. Using crosslinking-immunoprecipitation (CLIP) sequencing, we uncover several dramatic changes in the RNA-binding properties of Gag that occur during virion genesis, coincident with membrane binding, multimerization, and proteolytic maturation. Prior to assembly, and after virion assembly and maturation, the nucleocapsid domain of Gag preferentially binds to psi and Rev Response elements in the viral genome, and GU-rich mRNA sequences. However, during virion genesis, this specificity transiently changes in a manner that facilitates genome packaging; nucleocapsid binds to many sites on the HIV-1 genome and to mRNA sequences with a HIV-1-like, A-rich nucleotide composition. Additionally, we find that the matrix domain of Gag binds almost exclusively to specific tRNAs in the cytosol, and this association regulates Gag binding to cellular membranes.

引用

页码：1096 / 1109

页数：14

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