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.
Mouland
A J
AJ
Laboratory of Human Retrovirology, Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
Xu
H
H
Cui
H
H
Krueger
W
W
Munro
T P
TP
Prasol
M
M
Mercier
J
J
Rekosh
D
D
Smith
R
R
Barbarese
E
E
Cohen
E A
EA
Carson
J H
JH
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