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PMID: 21998393 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

NMR detection of structures in the HIV-1 5'-leader RNA that regulate genome packaging.

Science (New York, N.Y.) ·Vol. 334 ·No. 6053 ·2011-10-14 ·Pages 242-5

Lu K, Heng X, Garyu L, Monti S, Garcia EL, Kharytonchyk S, Dorjsuren B, Kulandaivel G, Jones S, Hiremath A, Divakaruni SS, LaCotti C, Barton S, Tummillo D, Hosic A, Edme K, Albrecht S, Telesnitsky A, Summers MF

Abstract

The 5'-leader of the HIV-1 genome regulates multiple functions during viral replication via mechanisms that have yet to be established. We developed a nuclear magnetic resonance approach that enabled direct detection of structural elements within the intact leader (712-nucleotide dimer) that are critical for genome packaging. Residues spanning the gag start codon (AUG) form a hairpin in the monomeric leader and base pair with residues of the unique-5' region (U5) in the dimer. U5:AUG formation promotes dimerization by displacing and exposing a dimer-promoting hairpin and enhances binding by the nucleocapsid (NC) protein, which is the cognate domain of the viral Gag polyprotein that directs packaging. Our findings support a packaging mechanism in which translation, dimerization, NC binding, and packaging are regulated by a common RNA structural switch.

MeSH Terms
5' Untranslated Regions Base Pairing Binding Sites Codon, Initiator Dimerization Genes, gag Genome, Viral HIV-1/genetics,physiology Human Immunodeficiency Virus Proteins/metabolism Mutagenesis, Site-Directed Nuclear Magnetic Resonance, Biomolecular Nucleic Acid Conformation Nucleocapsid Proteins/metabolism Protein Binding Protein Biosynthesis RNA, Viral/chemistry,genetics Virus Assembly gag Gene Products, Human Immunodeficiency Virus/metabolism
Chemicals
5' Untranslated Regions Codon, Initiator Human Immunodeficiency Virus Proteins Nucleocapsid Proteins RNA, Viral gag Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Lu Kun
Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), Baltimore, MD 21250, USA.
Heng Xiao
Garyu Lianko
Monti Sarah
Garcia Eric L
Kharytonchyk Siarhei
Dorjsuren Bilguujin
Kulandaivel Gowry
Jones Simonne
Hiremath Atheeth
Divakaruni Sai Sachin
LaCotti Courtney
Barton Shawn
Tummillo Daniel
Hosic Azra
Edme Kedy
Albrecht Sara
Telesnitsky Alice
Summers Michael F
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1210460
Published
2011-10-14
Pages
242-5
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3335204
Subset
IM
Grants
NIGMS NIH HHS · R01 GM42561 · United States
NIGMS NIH HHS · R25 GM055036-15 · United States
NIGMS NIH HHS · R01 GM042561-24 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · T34 GM008663 · United States
NIGMS NIH HHS · T32 GM007315 · United States
NIGMS NIH HHS · R25 GM055036-16 · United States
NIGMS NIH HHS · R01 GM042561-23 · United States
NIGMS NIH HHS · R25 GM055036 · United States
NIGMS NIH HHS · R01 GM042561-21 · United States
NIGMS NIH HHS · R01 GM042561 · United States
NIGMS NIH HHS · 2T34 GM008663 · United States
NIGMS NIH HHS · R25 GM55036 · United States
NIGMS NIH HHS · R01 GM042561-22 · United States
NIGMS NIH HHS · R25 GM055036-14 · United States
External Links
PubMed source DOI: 10.1126/science.1210460 PMC Full Text View journal details
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