TY - JOUR
T1 - Global changes in the RNA binding specificity of HIV-1 gag regulate virion genesis
AU - Kutluay, Sebla B.
AU - Zang, Trinity
AU - Blanco-Melo, Daniel
AU - Powell, Chelsea
AU - Jannain, David
AU - Errando, Manel
AU - Bieniasz, Paul D.
N1 - Funding Information:
We thank Markus Hafner and members of the Darnell and Tuschl labs for advice and helpful discussions. We thank Michael Summers for the diagram of the Ψ and RRE sequences in Figure 2 . S.B.K. was supported in part by an AmFAR Mathilde Krim Postdoctoral Fellowship. This work was supported by NIH grants R01AI501111 and P50GM103297.
Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2014/11/20
Y1 - 2014/11/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84911879495&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2014.09.057
DO - 10.1016/j.cell.2014.09.057
M3 - Article
C2 - 25416948
AN - SCOPUS:84911879495
SN - 0092-8674
VL - 159
SP - 1096
EP - 1109
JO - Cell
JF - Cell
IS - 5
ER -