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Cytoplasmic HIV-1 RNA is mainly transported by diffusion in the presence or absence of Gag protein
Biochemistry and Molecular Pharmacology Publications and Presentations
  • Jianbo Chen, National Cancer Institute
  • David Grünwald, University of Massachusetts Medical School
  • Luca Sardo, National Cancer Institute
  • Andrea Galli, National Cancer Institute
  • Sergey Plisov, National Cancer Institute
  • Olga A Nikolaitchik, National Cancer Institute
  • De Chen, Frederick National Laboratory for Cancer Research
  • Stephen Lockett, Frederick National Laboratory for Cancer Research
  • Daniel R. Larson, National Cancer Institute
  • Vinay K. Pathak, National Cancer Institute
  • Wei-Shau Hu, National Cancer Institute
UMMS Affiliation
RNA Therapeutics Institute and Department of Biochemistry and Molecular Pharmacology
Date
12-2-2014
Document Type
Article
Abstract
Full-length HIV-1 RNA plays a central role in viral replication by serving as the mRNA for essential viral proteins and as the genome packaged into infectious virions. Proper RNA trafficking is required for the functions of RNA and its encoded proteins; however, the mechanism by which HIV-1 RNA is transported within the cytoplasm remains undefined. Full-length HIV-1 RNA transport is further complicated when group-specific antigen (Gag) protein is expressed, because a significant portion of HIV-1 RNA may be transported as Gag-RNA complexes, whose properties could differ greatly from Gag-free RNA. In this report, we visualized HIV-1 RNA and monitored its movement in the cytoplasm by using single-molecule tracking. We observed that most of the HIV-1 RNA molecules move in a nondirectional, random-walk manner, which does not require an intact cytoskeletal structure, and that the mean-squared distance traveled by the RNA increases linearly with time, indicative of diffusive movement. We also observed that a single HIV-1 RNA molecule can move at various speeds when traveling through the cytoplasm, indicating that its movement is strongly affected by the immediate environment. To examine the effect of Gag protein on HIV-1 RNA transport, we analyzed the cytoplasmic HIV-1 RNA movement in the presence of sufficient Gag for virion assembly and found that HIV-1 RNA is still transported by diffusion with mobility similar to the mobility of RNAs unable to express functional Gag. These studies define a major mechanism of HIV-1 gene expression and resolve the long-standing question of how the RNA genome is transported to the assembly site.
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Citation: Chen J, Grunwald D, Sardo L, Galli A, Plisov S, Nikolaitchik OA, Chen D, Lockett S, Larson DR, Pathak VK, Hu WS. Cytoplasmic HIV-1 RNA is mainly transported by diffusion in the presence or absence of Gag protein. Proc Natl Acad Sci U S A. 2014 Dec 2;111(48):E5205-13. doi: 10.1073/pnas.1413169111. Link to article on publisher's site

Related Resources
Link to article in PubMed
Keywords
  • HIV-1,
  • RNA,
  • cytoplasm,
  • diffusion,
  • transport
PubMed ID
25404326
Update Submission
Initial Submission
Citation Information
Jianbo Chen, David Grünwald, Luca Sardo, Andrea Galli, et al.. "Cytoplasmic HIV-1 RNA is mainly transported by diffusion in the presence or absence of Gag protein" Vol. 111 Iss. 48 (2014) ISSN: 1091-6490
Available at: http://works.bepress.com/david_grunwald/18/