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PMID: 9298975 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Transportin-mediated nuclear import of heterogeneous nuclear RNP proteins.

The Journal of cell biology ·Vol. 138 ·No. 6 ·1997-09-22 ·Pages 1181-92

Siomi MC, Eder PS, Kataoka N, Wan L, Liu Q, Dreyfuss G

Abstract

Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is an abundant nuclear protein that plays an important role in pre-mRNA processing and mRNA export from the nucleus. A1 shuttles rapidly between the nucleus and the cytoplasm, and a 38-amino acid domain, M9, serves as the bidirectional transport signal of A1. Recently, a 90-kD protein, transportin, was identified as the mediator of A1 nuclear import. In this study, we show that transportin mediates the nuclear import of additional hnRNP proteins, including hnRNP F. We have also isolated and sequenced a novel transportin homolog, transportin2, which may differ from transportin1 in its substrate specificity. Immunostaining shows that transportin1 is localized both in the cytoplasm and the nucleoplasm, and nuclear rim staining is also observed. The nuclear localization of A1 is dependent on ongoing RNA polymerase II transcription. Interestingly, a pyruvate kinase-M9 fusion, which normally localizes in the nucleus, also accumulates in the cytoplasm when RNA polymerase II is inhibited. Thus, M9 itself is a specific sensor for transcription-dependent nuclear transport. Transportin1-A1 complexes can be isolated from the cytoplasm and the nucleoplasm, but transportin1 is not detectable in hnRNP complexes. RanGTP causes dissociation of A1-transportin1 complexes in vitro. Thus, it is likely that after nuclear import, A1 dissociates from transportin1 by RanGTP and becomes incorporated into hnRNP complexes, where A1 functions in pre-mRNA processing.

MeSH Terms
Animals Antibodies, Monoclonal Antibody Specificity Biological Transport/physiology Cell Nucleus/chemistry,enzymology Cytoplasm/chemistry,metabolism GTP-Binding Proteins/metabolism,pharmacology HeLa Cells Heterogeneous Nuclear Ribonucleoprotein A1 Heterogeneous-Nuclear Ribonucleoprotein Group A-B Heterogeneous-Nuclear Ribonucleoprotein Group F-H Heterogeneous-Nuclear Ribonucleoproteins Humans Karyopherins Mice Mice, Inbred BALB C Molecular Sequence Data Nuclear Proteins/analysis,chemistry,genetics,immunology,metabolism,pharmacology Pyruvate Kinase/metabolism RNA Precursors/metabolism Receptors, Cytoplasmic and Nuclear/chemistry,genetics,immunology,metabolism Ribonucleoproteins/metabolism Sequence Homology, Amino Acid Substrate Specificity Transcription, Genetic/physiology beta Karyopherins ran GTP-Binding Protein
Chemicals
Antibodies, Monoclonal Heterogeneous Nuclear Ribonucleoprotein A1 Heterogeneous-Nuclear Ribonucleoprotein Group A-B Heterogeneous-Nuclear Ribonucleoprotein Group F-H Heterogeneous-Nuclear Ribonucleoproteins Karyopherins Nuclear Proteins RNA Precursors Receptors, Cytoplasmic and Nuclear Ribonucleoproteins TNPO2 protein, human Tnpo2 protein, mouse beta Karyopherins Pyruvate Kinase GTP-Binding Proteins ran GTP-Binding Protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Siomi M C
Howard Hughes Medical Institute, and Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA.
Eder P S
Kataoka N
Wan L
Liu Q
Dreyfuss G
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.138.6.1181
Published
1997-09-22
Pages
1181-92
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2132560
Subset
IM
Databases
GENBANK
AF019039
External Links
PubMed source DOI: 10.1083/jcb.138.6.1181 PMC Full Text View journal details
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