Nuclear export of late HIV-1 mRNAs occurs via a cellular protein export pathway.
The Rev protein of HIV-1 is essential for the nuclear export of incompletely spliced viral mRNAs. This action depends on the mutationally defined Rev activation domain, which both binds the nucleoporin-like human cellular cofactor Rab/hRIP and also functions as a nuclear export signal. Protein kinase inhibitor alpha (PKI) also contains a potent nuclear export signal. However, PKI plays no role in nuclear RNA export and instead induces the nuclear export of a specific protein target, the catalytic subunit of cAMP-dependent protein kinase. Here, it is demonstrated that the nuclear export signal of PKI not only binds the Rab/hRIP cofactor specifically but also can effectively substitute for the Rev activation domain in mediating the nuclear export of HIV-1 mRNAs. We conclude that HIV-1 Rev and PKI act through an identical nuclear export pathway and that Rev, rather than using a dedicated RNA export pathway, is instead acting as an adaptor that allows viral mRNAs to access a cellular protein export pathway.
Fridell
R A
RA
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Bogerd
H P
HP
Cullen
B R
BR
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003587:Cytomegalovirus / Q000235:genetics; D004791:Enzyme Inhibitors; D015694:Gene Products, rev / Q000378:metabolism*; D016370:Gene Products, rex / Q000378:metabolism*; D005822:Genetic Vectors; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008322:Mammals; D008969:Molecular Sequence Data; D028861:Nuclear Pore Complex Proteins; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism*; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D015183:Restriction Mapping; D017386:Sequence Homology, Amino Acid; D054321:rev Gene Products, Human Immunodeficiency Virus
C119724:AGFG1 protein, human; D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D015694:Gene Products, rev; D016370:Gene Products, rex; D016655:HIV Core Protein p24; D047908:Intracellular Signaling Peptides and Proteins; D028861:Nuclear Pore Complex Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C015482:protein kinase modulator; D054321:rev Gene Products, Human Immunodeficiency Virus