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

@article{Lu2011NMRDO,
  title={NMR Detection of Structures in the HIV-1 5′-Leader RNA That Regulate Genome Packaging},
  author={Kun Lu and Xiao Heng and Lianko Garyu and Sarah Monti and Eric L. Garcia and Siarhei Kharytonchyk and Bilguujin Dorjsuren and Gowry Kulandaivel and Simonne Jones and Atheeth Hiremath and Sai Sachin Divakaruni and Courtney LaCotti and Shawn Barton and Daniel Tummillo and Azra Hosic and Kedy Edme and Sara Albrecht and Alice Telesnitsky and Michael F. Summers},
  journal={Science},
  year={2011},
  volume={334},
  pages={242 - 245}
}
The 5'-leader of the HIV-1 genome regulates multiple functions during viral replication via mechanisms that have yet to be established. [...] Key Method 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…Expand
Structure of the HIV-1 RNA packaging signal
TLDR
The structure shows how the 5′ leader binds to the HIV protein that directs packaging, how unspliced dimeric genomes are selected for packaging, and how translation is suppressed when the genome dimerizes. Expand
Structural investigation of HIV-1 genomic RNA dimerization process reveals a role for the Major Splice-site Donor stem loop.
TLDR
It is shown that swapping the Gag open reading frame (ORF) by reporter genes interferes with dimers formation efficiency and this data support a recently proposed model in which intramolecular base pairings are important determinants for the dimerization process. Expand
Identification of a minimal region of the HIV-1 5'-leader required for RNA dimerization, NC binding, and packaging.
TLDR
This work generated HIV-1 5'-L RNAs containing mutations and deletions designed to eliminate substructures without perturbing the overall structure of the leader and examined effects of the mutations on RNA dimerization, NC binding, and packaging. Expand
A Short Sequence Motif in the 5′ Leader of the HIV-1 Genome Modulates Extended RNA Dimer Formation and Virus Replication*
TLDR
Characterization of the mutant and revertant RNA molecules and the corresponding viruses confirmed the correlation between in vitro ED RNA dimer formation and efficient virus replication, thus indicating that the ED structure is important for HIV-1 replication. Expand
NMR detection of intermolecular interaction sites in the dimeric 5′-leader of the HIV-1 genome
TLDR
Two studies illustrate the utility of 2H-edited NMR for determining the structures and folding kinetics of relatively large RNAs and indicate that a kissing dimer-mediated structure exists only transiently and readily converts to the extended interface structure, even in the absence of the HIV-1 nucleocapsid protein or other RNA chaperones. Expand
Identification of the initial nucleocapsid recognition element in the HIV-1 RNA packaging signal
TLDR
NMR studies reveal that a recently discovered small-molecule inhibitor of HIV-1 RNA packaging that appears to function by stabilizing the structure of the leader binds directly to the [UUUU]:[GGAG] helix. Expand
NMR Studies of the Structure and Function of the HIV-1 5′-Leader
TLDR
NMR spectroscopy approaches have been developed that enable direct detection of intra- and inter-molecular interactions within the intact leader, providing detailed insights into the structural determinants and mechanisms that regulate HIV-1 genome packaging and function. Expand
Structure and sequence motifs in the HIV-1 RNA genome
TLDR
It is demonstrated that all essential RNA and enzyme components for reverse transcription are present in these virions and hypothesize that the spatiotemporal regulation of reverse transcription is disturbed by the mislocalization of these components. Expand
New Structure Sheds Light on Selective HIV-1 Genomic RNA Packaging
TLDR
This study serves as the basis for characterizing large RNA structures using novel NMR techniques, and as a major advance toward understanding how the HIV-1 gRNA is selectively packaged. Expand
In Vivo SELEX of Single-Stranded Domains in the HIV-1 Leader RNA
TLDR
The in vivo SELEX approach probed the sequence space in these regions that is compatible with efficient HIV-1 replication and analyzed the impact on the RNA secondary structure of the leader RNA, showing a strong sequence requirement for the DIS hairpin flanking regions. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 50 REFERENCES
RNA Structure and Packaging Signals in the 5′ Leader Region of the Human Immunodeficiency Virus Type 1 Genome
TLDR
A mutational analysis is reported identifying at least three separate loci within the U5-PBS region which, when mutated, impair both HIV-1 packaging specificity and infectivity in a single-round proviral assay. Expand
RNA interactions in the 5' region of the HIV-1 genome.
TLDR
This work used a recently developed RNA folding algorithm (Pfold) to predict the common secondary structure of an alignment of 20 divergent HIV-1 sequences and identified a novel tertiary interaction within the PBS hairpin structure. Expand
Structural determinants and mechanism of HIV-1 genome packaging.
TLDR
Efforts to identify the molecular determinants and mechanism of human immunodeficiency virus type 1 genome packaging are reviewed. Expand
Functional sites in the 5' region of human immunodeficiency virus type 1 RNA form defined structural domains.
TLDR
The conformation of the first 500 nucleotides covering the RNA leader and the 5' gag coding sequences of HIV-MAL, using chemical probing, shows the structural versatility of this region and suggests two mutually exclusive structures could modulate the different functions involving this domain. Expand
Two alternating structures of the HIV-1 leader RNA.
TLDR
It is proposed that this structural polymorphism of the HIV-1 leader RNA acts as a molecular switch in the viral replication cycle, facilitated by the viral nucleocapsid protein NC. Expand
A Novel Long Distance Base-pairing Interaction in Human Immunodeficiency Virus Type 1 RNA Occludes the Gag Start Codon*
TLDR
Evidence is presented that the full-length 5′-UTR also adopts the LDI and BMH conformations, and the presence of this U5-AUG duplex may influence translation of the Gag protein because it occludes the start codon of theGag open reading frame. Expand
RNA secondary structure and binding sites for gag gene products in the 5' packaging signal of human immunodeficiency virus type 1
TLDR
Chemical and RNase accessibility mapping, coupled with computerized sequence analysis, suggested a model for psi RNA structure comprising four independent stem-loops, which revealed that RNAs corresponding to three of these hypothetical stem-Loops can each function as a independent Gag binding site and that each is bound with approximately fourfold-lower apparent affinity than the full-length psi locus. Expand
Role of the 5' TAR stem--loop and the U5-AUG duplex in dimerization of HIV-1 genomic RNA.
TLDR
A role is identified for the 5' transactivation response element (5' TAR) and a contribution of a long-distance base pairing between a sequence located at the beginning of the U5 region and nucleotides surrounding the AUG Gag initiation codon in the resulting intra- or intermolecular duplex is called the U 5-AUG duplex. Expand
The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures
TLDR
The HIV-1 E/psi region is a multipartite element composed of specific and functional RNA secondary structures, and a subset of the hydrogen-bonded base pairs within the stems of the hairpins is likely to be required for function in cis. Expand
HIV-1 RNA packaging.
  • A. Lever
  • Biology, Medicine
  • Advances in pharmacology
  • 2007
TLDR
This chapter focuses on the concept of human immunodeficiency virus type 1 (HIV‐1) RNA packaging, a remarkable process by which the virus negotiates the negotiation of a minority species of mRNA through a particular cellular pathway to become its genome. Expand
...
1
2
3
4
5
...