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PMID: 16478985 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The UL69 transactivator protein of human cytomegalovirus interacts with DEXD/H-Box RNA helicase UAP56 to promote cytoplasmic accumulation of unspliced RNA.

Molecular and cellular biology ·Vol. 26 ·No. 5 ·2006-03-00 ·Pages 1631-43

Lischka P, Toth Z, Thomas M, Mueller R, Stamminger T

Abstract

The UL69 gene product of human cytomegalovirus belongs to a family of regulatory proteins conserved among all herpesviruses that have in part been characterized as posttranscriptional transactivators participating in the nuclear export of RNA. Recent experiments suggested that pUL69 also acts as a posttranscriptional activator since it was demonstrated that nucleocytoplasmic shuttling via a CRM1-independent nuclear export signal is a prerequisite for its stimulatory effect on gene expression. Based on these findings we initiated studies to investigate the role of pUL69 in mRNA export and demonstrate that pUL69 efficiently promotes the cytoplasmic accumulation of unspliced RNA. Furthermore, we show that this pUL69 activity is linked to the cellular mRNA export machinery by direct protein interaction with the highly related DEXD/H-box RNA helicases UAP56 and URH49. Particularly, we identified a 12-amino-acid domain within the N terminus of pUL69 which is required for binding to UAP56 and URH49, and we could demonstrate that UAP56 interaction and nucleocytoplasmic shuttling are both prerequisites for pUL69-mediated mRNA export. Thus, we identified a novel cellular target which provides a herpesviral regulatory protein with access to a conserved cellular transport system in order to promote nuclear export of unspliced RNA.

MeSH Terms
Active Transport, Cell Nucleus Amino Acid Motifs Amino Acid Sequence Cell Nucleus/genetics,metabolism Cells, Cultured Cytomegalovirus/genetics,metabolism,pathogenicity Cytoplasm/genetics,metabolism DEAD-box RNA Helicases DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics,metabolism HeLa Cells/virology Humans Karyopherins/genetics,metabolism Molecular Sequence Data Mutation RNA Helicases/genetics,metabolism RNA Splicing RNA, Messenger/genetics,metabolism RNA, Viral/genetics,metabolism Receptors, Cytoplasmic and Nuclear/genetics,metabolism Trans-Activators/genetics,metabolism Viral Proteins/genetics,metabolism
Chemicals
Karyopherins RNA, Messenger RNA, Viral Receptors, Cytoplasmic and Nuclear Trans-Activators Viral Proteins exportin 1 protein pUL69 protein, Human herpesvirus 5 DDX39A protein, human DDX39B protein, human DEAD-box RNA Helicases RNA Helicases APEX1 protein, human DNA-(Apurinic or Apyrimidinic Site) Lyase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Lischka Peter
Institut für Klinische und Molekulare Virologie, Universität Erlangen-Nürnberg, Schlossgarten 4, 91054 Erlangen, Germany. thomas.stamminger@viro.med.uni-erlangen.de.
Toth Zsolt
Thomas Marco
Mueller Regina
Stamminger Thomas
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.26.5.1631-1643.2006
Email
thomas.stamminger@viro.med.uni-erlangen.de
Published
2006-03-00
Pages
1631-43
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1430265
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.26.5.1631-1643.2006 PMC Full Text View journal details
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