title: NMR detection of structures in the HIV-1 5'-leader RNA that regulate genome packaging.
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.
authors: Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), Baltimore, MD 21250, USA.
authors: Kun
authors: K
authors: Lu
authors: Xiao
authors: X
authors: Heng
authors: Lianko
authors: L
authors: Garyu
authors: Sarah
authors: S
authors: Monti
authors: Eric L
authors: EL
authors: Garcia
authors: Siarhei
authors: S
authors: Kharytonchyk
authors: Bilguujin
authors: B
authors: Dorjsuren
authors: Gowry
authors: G
authors: Kulandaivel
authors: Simonne
authors: S
authors: Jones
authors: Atheeth
authors: A
authors: Hiremath
authors: Sai Sachin
authors: SS
authors: Divakaruni
authors: Courtney
authors: C
authors: LaCotti
authors: Shawn
authors: S
authors: Barton
authors: Daniel
authors: D
authors: Tummillo
authors: Azra
authors: A
authors: Hosic
authors: Kedy
authors: K
authors: Edme
authors: Sara
authors: S
authors: Albrecht
authors: Alice
authors: A
authors: Telesnitsky
authors: Michael F
authors: MF
authors: Summers
mesh_terms: D020121:5' Untranslated Regions; D020029:Base Pairing; D001665:Binding Sites; D018387:Codon, Initiator; D019281:Dimerization; D015750:Genes, gag; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D019590:Nucleocapsid Proteins / Q000378:metabolism; D011485:Protein Binding; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics*; D019065:Virus Assembly; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D018387:Codon, Initiator; D054298:Human Immunodeficiency Virus Proteins; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus