Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K

Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular...

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Hlavní autoři: Bogerd, Hal P., Wiegand, Heather L., Yang, Jin, Cullen, Bryan R.
Médium: Článek
Jazyk:en
Vydáno: American Society for Microbiology 2000
Témata:
Replication
On-line přístup:https://ncbi.nlm.nih.gov/pmc/articles/PMC112363/
https://ncbi.nlm.nih.gov/pubmed/11000203
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spelling pubmed-1123632002-09-13 Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K Bogerd, Hal P. Wiegand, Heather L. Yang, Jin Cullen, Bryan R. J Virol Replication Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the ∼25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function. American Society for Microbiology 2000-10 /pmc/articles/PMC112363/ /pubmed/11000203 Text en Copyright © 2000, American Society for Microbiology
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Replication
spellingShingle Replication
Bogerd, Hal P.
Wiegand, Heather L.
Yang, Jin
Cullen, Bryan R.
Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K
description Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the ∼25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function.
author Bogerd, Hal P.
Wiegand, Heather L.
Yang, Jin
Cullen, Bryan R.
author_facet Bogerd, Hal P.
Wiegand, Heather L.
Yang, Jin
Cullen, Bryan R.
author_sort Bogerd, Hal P.
title Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K
title_short Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K
title_full Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K
title_fullStr Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K
title_full_unstemmed Mutational Definition of Functional Domains within the Rev Homolog Encoded by Human Endogenous Retrovirus K
title_sort mutational definition of functional domains within the rev homolog encoded by human endogenous retrovirus k
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2000
url https://ncbi.nlm.nih.gov/pmc/articles/PMC112363/
https://ncbi.nlm.nih.gov/pubmed/11000203
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