TY - JOUR
T1 - NMR detection of structures in the HIV-1 5′-leader RNA that regulate genome packaging
AU - Lu, Kun
AU - Heng, Xiao
AU - Garyu, Lianko
AU - Monti, Sarah
AU - Garcia, Eric L.
AU - Kharytonchyk, Siarhei
AU - Dorjsuren, Bilguujin
AU - Kulandaivel, Gowry
AU - Jones, Simonne
AU - Hiremath, Atheeth
AU - Divakaruni, Sai Sachin
AU - LaCotti, Courtney
AU - Barton, Shawn
AU - Tummillo, Daniel
AU - Hosic, Azra
AU - Edme, Kedy
AU - Albrecht, Sara
AU - Telesnitsky, Alice
AU - Summers, Michael F.
PY - 2011/10/14
Y1 - 2011/10/14
N2 - 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.
AB - 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.
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U2 - 10.1126/science.1210460
DO - 10.1126/science.1210460
M3 - Article
C2 - 21998393
AN - SCOPUS:80054114304
SN - 0036-8075
VL - 334
SP - 242
EP - 245
JO - Science
JF - Science
IS - 6053
ER -
