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RNA structure. Structure of the HIV-1 RNA packaging signal
Sarah C Keane1, Xiao Heng1, Kun Lu1
1Howard Hughes Medical Institute (HHMI) and Department of Chemistry and Biochemistry, University of Maryland Baltimore County (UMBC), 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Science (New York, N.Y.)
|May 23, 2015
Summary
The HIV-1 RNA leader forms a unique structure that controls viral packaging. This structure exposes key guanosines for Gag protein binding, promoting viral assembly and genome selection.
Area of Science:
- Molecular Biology
- Structural Biology
- Virology
Background:
- The 5' leader of the Human Immunodeficiency Virus type 1 (HIV-1) genome possesses conserved elements crucial for selective packaging of unspliced, dimeric viral RNA into new viral particles.
- Understanding these elements is vital for comprehending HIV-1 replication and for developing antiviral strategies.
Purpose of the Study:
- To determine the three-dimensional structure of a 155-nucleotide region of the HIV-1 leader, known as the core encapsidation signal (Ψ(CES)).
- To elucidate how this RNA structure facilitates selective viral RNA packaging, Gag protein binding, and regulation of viral translation.
Main Methods:
- Utilized a (2)H-edited nuclear magnetic resonance (NMR) spectroscopy approach to analyze the RNA structure.
- Investigated the structural features of the Ψ(CES) region, focusing on base pairing and nucleotide accessibility.
Main Results:
- The HIV-1 Ψ(CES) RNA region adopts an unexpected tandem three-way junction conformation.
- This structure sequesters essential sites for major splice donor and translation initiation.
- Key guanosines, critical for RNA packaging and Gag protein interaction, are exposed within helical junctions.
Conclusions:
- The determined RNA structure provides a molecular basis for understanding selective viral genome packaging in HIV-1.
- The structure explains the mechanism of translation attenuation and enhanced Gag binding.
- This structural insight is essential for understanding how unspliced dimeric genomes are selected during viral assembly.
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