Three-dimensional RNA Structure of the Major HIV-1 Packaging Signal Region

Overview

Journal Structure

Publisher Cell Press

Specialties Biochemistry
Biotechnology
Cell Biology
Molecular Biology

Date 2013 May 21

PMID 23685210

Citations 24

Authors

James D Stephenson

Haitao Li

Julia C Kenyon

Martyn Symmons

Dave Klenerman

Andrew M L Lever

Affiliations

Soon will be listed here.

Abstract

HIV-1 genomic RNA has a noncoding 5' region containing sequential conserved structural motifs that control many parts of the life cycle. Very limited data exist on their three-dimensional (3D) conformation and, hence, how they work structurally. To assemble a working model, we experimentally reassessed secondary structure elements of a 240-nt region and used single-molecule distances, derived from fluorescence resonance energy transfer, between defined locations in these elements as restraints to drive folding of the secondary structure into a 3D model with an estimated resolution below 10 Å. The folded 3D model satisfying the data is consensual with short nuclear-magnetic-resonance-solved regions and reveals previously unpredicted motifs, offering insight into earlier functional assays. It is a 3D representation of this entire region, with implications for RNA dimerization and protein binding during regulatory steps. The structural information of this highly conserved region of the virus has the potential to reveal promising therapeutic targets.

Citing Articles

Recent advances in RNA structurome.

Xu B, Zhu Y, Cao C, Chen H, Jin Q, Li G Sci China Life Sci. 2022; 65(7):1285-1324.

PMID: 35717434 PMC: 9206424. DOI: 10.1007/s11427-021-2116-2.

Evaluating RNA Structural Flexibility: Viruses Lead the Way.

Fairman C, Lever A, Kenyon J Viruses. 2021; 13(11).

PMID: 34834937 PMC: 8624864. DOI: 10.3390/v13112130.

Intrinsic conformational dynamics of the HIV-1 genomic RNA 5'UTR.

Brigham B, Kitzrow J, Reyes J, Musier-Forsyth K, Munro J Proc Natl Acad Sci U S A. 2019; 116(21):10372-10381.

PMID: 31068467 PMC: 6534999. DOI: 10.1073/pnas.1902271116.

RNA Structure-A Neglected Puppet Master for the Evolution of Virus and Host Immunity.

Smyth R, Negroni M, Lever A, Mak J, Kenyon J Front Immunol. 2018; 9:2097.

PMID: 30283444 PMC: 6156135. DOI: 10.3389/fimmu.2018.02097.

An RNA-binding compound that stabilizes the HIV-1 gRNA packaging signal structure and specifically blocks HIV-1 RNA encapsidation.

Ingemarsdotter C, Zeng J, Long Z, Lever A, Kenyon J Retrovirology. 2018; 15(1):25.

PMID: 29540207 PMC: 5853050. DOI: 10.1186/s12977-018-0407-4.

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