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PMID: 14981248 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transportin2 functions as importin and mediates nuclear import of HuR.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 9 ·2004-03-02 ·Pages 2918-23

Güttinger S, Mühlhäusser P, Koller-Eichhorn R, Brennecke J, Kutay U

Abstract

The RanGTP-binding nuclear transport receptors transportin1 (TRN1) and transportin2 (TRN2) are highly similar in sequence but are reported to function in nuclear import and export, respectively. Here we show that TRN2 possesses properties of a nuclear import receptor. TRN1/2 both interacted with a similar set of RNA-binding proteins in a RanGTP-sensitive manner. TRN2 bound RanGTP with high affinity, a feature of nuclear import receptors. As expected of an import complex, RanGTP also disrupted the interaction between TRN2 and HuR, an RNA-binding protein previously described as a TRN2 export substrate. The HuR nucleocytoplasmic shuttling signal, a sequence resembling the M9 nuclear import signal of hnRNP A1, was necessary and sufficient for TRN-mediated nuclear import of HuR in vitro. Finally, crosscompetition experiments demonstrated that HuR nucleocytoplasmic shuttling signal and M9 are imported along redundant pathways involving TRN1/2, substantiating the function of TRN2 in nuclear import.

MeSH Terms
Amino Acid Sequence Animals Antibodies/chemistry Antigens, Surface/metabolism Cell Nucleus/metabolism Cloning, Molecular DNA, Complementary/genetics ELAV Proteins ELAV-Like Protein 1 HeLa Cells Humans Molecular Sequence Data Poly(A)-Binding Proteins/metabolism Protein Transport RNA-Binding Proteins/metabolism Rabbits Receptors, Cytoplasmic and Nuclear/genetics,metabolism Recombinant Proteins/metabolism Restriction Mapping Vascular Endothelial Growth Factor A/metabolism beta Karyopherins/genetics,metabolism
Chemicals
Antibodies Antigens, Surface DNA, Complementary ELAV Proteins ELAV-Like Protein 1 ELAVL1 protein, human Poly(A)-Binding Proteins RNA-Binding Proteins Receptors, Cytoplasmic and Nuclear Recombinant Proteins TNPO2 protein, human Vascular Endothelial Growth Factor A beta Karyopherins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Güttinger Stephan
Swiss Federal Institute of Technology, Institute of Biochemistry, HPM F11.1, 8093 Zürich, Switzerland.
Mühlhäusser Petra
Koller-Eichhorn Roland
Brennecke Julius
Kutay Ulrike
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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.0400342101
Published
2004-03-02
Epub
2004-00-23
Pages
2918-23
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC365720
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0400342101 PMC Full Text View journal details
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