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NMR Detection of Structures in the HIV-1 5′-Leader RNA That Regulate Genome Packaging

2011; American Association for the Advancement of Science; Volume: 334; Issue: 6053 Linguagem: Inglês

10.1126/science.1210460

1095-9203

Kun Lu, Xiao Heng, Lianko Garyu, Sarah Monti, Eric L. Garcia, Siarhei Kharytonchyk, Bilguujin Dorjsuren, Gowry Kulandaivel, Simonne Jones, Atheeth Hiremath, Sai Sachin Divakaruni, Courtney LaCotti, Shawn Barton, Daniel Tummillo, Azra Hosic, Kedy Edme, Sara E. Albrecht, Alice Telesnitsky, Michael F. Summers,

RNA Research and Splicing

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.