Retroviral mRNA nuclear export elements regulate protein function and virion assembly.
Rodent cells are notable for their inability to support normal assembly of HIV particles. In this report, we address possible causes for this defect by considering the hypothesis that mRNA-associated events occurring in the nucleus can regulate the activity of their encoded proteins in the cytoplasm. We show that altering the RNA nuclear export element used by HIV gag-pol mRNA from the Rev response element to the constitutive transport element restores both the trafficking of Gag to cellular membranes and efficient HIV assembly in murine cells. These results suggest that two phases of the HIV life cycle, RNA export and capsid assembly, that have hitherto been regarded as distinct are, in fact, linked. Thus, protein function and fate may depend upon the full and precise history of its encoding mRNA.
Swanson
Chad M
CM
Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Puffer
Bridget A
BA
Ahmad
K Muneer
KM
Doms
Robert W
RW
Malim
Michael H
MH
D016475:3T3 Cells; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D015694:Gene Products, rev / Q000235:genetics / Q000378:metabolism; D015750:Genes, gag / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007211:Indoles; D051379:Mice; D018613:Microscopy, Confocal; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D012235:Rhodamines; D014615:Vaccinia / Q000235:genetics; D014771:Virion / Q000378:metabolism*
D005456:Fluorescent Dyes; D015694:Gene Products, rev; D007211:Indoles; D011506:Proteins; D012333:RNA, Messenger; D012367:RNA, Viral; D012235:Rhodamines; C009434:tetramethylrhodamine isothiocyanate; C007293:DAPI