Rev-mediated nuclear export of RNA is dominant over nuclear retention and is coupled to the Ran-GTPase cycle.
The human immunodeficiency virus type-1 Rev protein induces the nuclear export of intron-containing viral mRNAs that harbor its binding site, the Rev response element (RRE). A leucine-rich region of Rev, the activation domain, is essential for function and has been shown to be a nuclear export signal (NES). Although Rev exports viral RNAs that resemble cellular mRNAs, competition studies performed using microinjected Xenopus laevis oocytes have previously indicated that Rev utilizes a non-mRNA export pathway. Here, we show that Rev is able to induce the export of both spliceable and non-spliceable RRE-containing pre-mRNAs and that this activity is not dependent on the location of the RRE within the RNA. Importantly, even RNA molecules of different classes, such as U3 snoRNA and U6 snRNA, which are retained in the nucleus by non-pre-mRNA mechanisms, are exported to the cytoplasm in response to Rev. Consistent with the notion that Rev-mediated export of RRE-containing RNA is mechanistically distinct from the export of processed cellular mRNA, a chimeric Rev protein in which its NES is replaced by the NES of hnRNP A1 does not induce the export of a Rev-responsive mRNA. Finally, we demonstrate that Rev/RRE-activated RNA export is, like other nuclear export pathways, linked to the Ran-GTPase cycle.
Fischer
U
U
Institut für Molekularbiologie und Tumorforschung, Marburg, Germany. ufischer@biochem.mpg.de
Pollard
V W
VW
Lührmann
R
R
Teufel
M
M
Michael
M W
MW
Dreyfuss
G
G
Malim
M H
MH
D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D016384:Consensus Sequence / Q000235:genetics; D005091:Exons / Q000235:genetics; D015694:Gene Products, rev / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015696:Gene Products, tat / Q000235:genetics; D015497:HIV-1 / Q000235:genetics; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007438:Introns / Q000235:genetics; D009154:Mutation; D009865:Oocytes / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing / Q000235:genetics; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D020537:RNA, Small Nucleolar / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D014982:Xenopus laevis; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D015696:Gene Products, tat; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012322:RNA Precursors; D012342:RNA, Small Nuclear; D020537:RNA, Small Nucleolar; C117378:RNA, U3 small nucleolar; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D054321:rev Gene Products, Human Immunodeficiency Virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D012313:RNA; D020931:ran GTP-Binding Protein