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Cell. 2014 Nov 20;159(5):1096-1109. doi: 10.1016/j.cell.2014.09.057. Epub 2014 Nov 6.

Global changes in the RNA binding specificity of HIV-1 gag regulate virion genesis.

Author information

1
Laboratory of Retrovirology, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
2
Laboratory of Retrovirology, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA; Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
3
Department of Physics and Astronomy, Barnard College, Columbia University, New York, NY 10027, USA.
4
Laboratory of Retrovirology, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA; Howard Hughes Medical Institute, Aaron Diamond AIDS Research Center, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. Electronic address: pbienias@adarc.org.

Abstract

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.

Comment in

PMID:
25416948
PMCID:
PMC4247003
DOI:
10.1016/j.cell.2014.09.057
[Indexed for MEDLINE]
Free PMC Article

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