Open AccessNuclear export of late HIV-1 mRNAs occurs via a cellular protein export pathway.
Author(s) -
Robert A. Fridell,
Hal P. Bogerd,
Bryan R. Cullen
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.9.4421
Subject(s) - nuclear export signal , nuclear transport , microbiology and biotechnology , rab , nuclear protein , nuclear localization sequence , signal transducing adaptor protein , protein subunit , rna binding protein , biology , protein kinase a , cell nucleus , rna , signal transduction , kinase , biochemistry , gene , cytoplasm , transcription factor , gtpase
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.