RNA trafficking signals in human immunodeficiency virus type 1.
Intracellular trafficking of retroviral RNAs is a potential mechanism to target viral gene expression to specific regions of infected cells. Here we show that the human immunodeficiency virus type 1 (HIV-1) genome contains two sequences similar to the hnRNP A2 response element (A2RE), a cis-acting RNA trafficking sequence that binds to the trans-acting trafficking factor, hnRNP A2, and mediates a specific RNA trafficking pathway characterized extensively in oligodendrocytes. The two HIV-1 sequences, designated A2RE-1, within the major homology region of the gag gene, and A2RE-2, in a region of overlap between the vpr and tat genes, both bind to hnRNP A2 in vitro and are necessary and sufficient for RNA transport in oligodendrocytes in vivo. A single base change (A8G) in either sequence reduces hnRNP A2 binding and, in the case of A2RE-2, inhibits RNA transport. A2RE-mediated RNA transport is microtubule and hnRNP A2 dependent. Differentially labelled gag and vpr RNAs, containing A2RE-1 and A2RE-2, respectively, coassemble into the same RNA trafficking granules and are cotransported to the periphery of the cell. tat RNA, although it contains A2RE-2, is not transported as efficiently as vpr RNA. An A2RE/hnRNP A2-mediated trafficking pathway for HIV RNA is proposed, and the role of RNA trafficking in targeting HIV gene expression is discussed.
Laboratory of Human Retrovirology, Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
A J
AJ
Mouland
H
H
Xu
H
H
Cui
W
W
Krueger
T P
TP
Munro
M
M
Prasol
J
J
Mercier
D
D
Rekosh
R
R
Smith
E
E
Barbarese
E A
EA
Cohen
J H
JH
Carson
D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D002478:Cells, Cultured; D015683:Gene Products, gag / Q000235:genetics; D016336:Gene Products, vpr / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D051379:Mice; D008967:Molecular Biology / Q000379:methods; D008969:Molecular Sequence Data; D009836:Oligodendroglia / Q000166:cytology / Q000821:virology*; D010446:Peptide Fragments / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis* / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics*; D012261:Ribonucleoproteins / Q000235:genetics; D054325:vpr Gene Products, Human Immunodeficiency Virus
D015683:Gene Products, gag; D016336:Gene Products, vpr; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D010446:Peptide Fragments; D012367:RNA, Viral; D012261:Ribonucleoproteins; C439768:hnRNP A2; D054325:vpr Gene Products, Human Immunodeficiency Virus; C422457:vpr peptide (13-33), Human immunodeficiency virus 1