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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line
  • Chromatin Immunoprecipitation
  • Genes, env
  • HIV-1 / physiology*
  • Humans
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RNA, Transfer / metabolism
  • RNA, Viral / metabolism*
  • Virus Assembly
  • gag Gene Products, Human Immunodeficiency Virus / chemistry
  • gag Gene Products, Human Immunodeficiency Virus / metabolism*


  • RNA, Viral
  • gag Gene Products, Human Immunodeficiency Virus
  • RNA, Transfer

Associated data

  • GEO/GSE61508