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

被引：210

作者：

Lu, Kun ^{[2
,3
]}

Heng, Xiao ^{[2
,3
]}

Garyu, Lianko ^{[2
,3
]}

Monti, Sarah ^{[2
,3
]}

Garcia, Eric L. ^{[1
]}

Kharytonchyk, Siarhei ^{[1
]}

Dorjsuren, Bilguujin ^{[2
,3
]}

Kulandaivel, Gowry ^{[2
,3
]}

Jones, Simonne ^{[2
,3
]}

Hiremath, Atheeth ^{[2
,3
]}

Divakaruni, Sai Sachin ^{[2
,3
]}

LaCotti, Courtney ^{[2
,3
]}

Barton, Shawn ^{[2
,3
]}

Tummillo, Daniel ^{[2
,3
]}

Hosic, Azra ^{[2
,3
]}

Edme, Kedy ^{[2
,3
]}

Albrecht, Sara ^{[2
,3
]}

Telesnitsky, Alice ^{[1
]}

Summers, Michael F. ^{[2
,3
]}

机构：

[1] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA

[2] Univ Maryland Baltimore Cty, Howard Hughes Med Inst, Baltimore, MD 21250 USA

[3] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA

来源：

SCIENCE | 2011年 / 334卷 / 6053期

关键词：

SECONDARY STRUCTURE; GAG GENE; REGION; SIGNAL; SITE; RETROVIRUSES; DIMERIZATION; TRANSLATION;

D O I：

10.1126/science.1210460

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：242 / 245

页数：4

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