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PMID: 8633082 Published · ppublish English Journal Article

Nuclear export of late HIV-1 mRNAs occurs via a cellular protein export pathway.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 93 ·No. 9 ·1996-04-30 ·Pages 4421-4

Fridell RA, Bogerd HP, Cullen BR

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Carrier Proteins/metabolism Cell Nucleus/metabolism Cytomegalovirus/genetics Enzyme Inhibitors Gene Products, rev/metabolism Gene Products, rex/metabolism Genetic Vectors HIV Core Protein p24/biosynthesis HIV-1/metabolism Humans Intracellular Signaling Peptides and Proteins Mammals Molecular Sequence Data Nuclear Pore Complex Proteins Promoter Regions, Genetic Protein Kinase Inhibitors RNA Splicing RNA, Messenger/metabolism RNA, Viral/metabolism RNA-Binding Proteins Restriction Mapping Sequence Homology, Amino Acid rev Gene Products, Human Immunodeficiency Virus
Chemicals
AGFG1 protein, human Carrier Proteins Enzyme Inhibitors Gene Products, rev Gene Products, rex HIV Core Protein p24 Intracellular Signaling Peptides and Proteins Nuclear Pore Complex Proteins Protein Kinase Inhibitors RNA, Messenger RNA, Viral RNA-Binding Proteins protein kinase modulator rev Gene Products, Human Immunodeficiency Virus
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Fridell R A
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Bogerd H P
Cullen B R
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31 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.93.9.4421
Published
1996-04-30
Pages
4421-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC39553
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.93.9.4421 PMC Full Text View journal details
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