Identification of a minimal region of the HIV-1 5′-leader required for RNA dimerization, NC binding, and packaging

Xiao Heng, Siarhei Kharytonchyk, Eric L. Garcia, Kun Lu, Sai Sachin Divakaruni, Courtney Lacotti, Kedy Edme, Alice Telesnitsky, Michael F. Summers

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Assembly of human immunodeficiency virus type 1 (HIV-1) particles is initiated in the cytoplasm by the formation of a ribonucleoprotein complex comprising the dimeric RNA genome and a small number of viral Gag polyproteins. Genomes are recognized by the nucleocapsid (NC) domains of Gag, which interact with packaging elements believed to be located primarily within the 5′-leader (5′-L) of the viral RNA. Recent studies revealed that the native 5′-L exists as an equilibrium of two conformers, one in which dimer-promoting residues and NC binding sites are sequestered and packaging is attenuated, and one in which these sites are exposed and packaging is promoted. To identify the elements within the dimeric 5′-L that are important for packaging, we generated HIV-1 5′-L RNAs containing mutations and deletions designed to eliminate substructures without perturbing the overall structure of the leader and examined effects of the mutations on RNA dimerization, NC binding, and packaging. Our findings identify a 159-residue RNA packaging signal that possesses dimerization and NC binding properties similar to those of the intact 5′-L and contains elements required for efficient RNA packaging.

Original languageEnglish
Pages (from-to)224-239
Number of pages16
JournalJournal of Molecular Biology
Volume417
Issue number3
DOIs
StatePublished - Mar 30 2012

Bibliographical note

Funding Information:
This work was supported by a grant from the National Institute of General Medical Sciences ( GM 42561 ). K.E. was supported by a grant from the National Institute of General Medical Sciences for enhancing minority access to research careers ( MARC U⁎STAR 2T34 GM008663 ). We thank the Howard Hughes Medical Institute staff at the University of Maryland Baltimore County for technical assistance.

Keywords

  • ITC
  • RNA structure
  • diploid genome packaging
  • nucleocapsid protein
  • retrovirus assembly

ASJC Scopus subject areas

  • Molecular Biology
  • Biophysics
  • Structural Biology

Fingerprint

Dive into the research topics of 'Identification of a minimal region of the HIV-1 5′-leader required for RNA dimerization, NC binding, and packaging'. Together they form a unique fingerprint.

Cite this