Document Detail

Efficient NES-dependent protein nuclear export requires ongoing synthesis and export of mRNAs.
MedLine Citation:
PMID:  15212955     Owner:  NLM     Status:  MEDLINE    
The mechanisms regulating nuclear export of proteins are not fully understood. To investigate whether the efficiency of protein nuclear export may depend on ongoing RNA synthesis and/or mRNA nuclear export, we used a microinjection approach with a fluorescent reporter protein containing a nuclear export signal (NES) and scored protein export in human fibroblasts under conditions when the synthesis or export of mRNAs was inhibited. We show that inhibition of transcription significantly attenuated generic NES-dependent nuclear export. Furthermore, digestion of endogenous nuclear RNAs by co-microinjection of RNAse A inhibited NES-dependent nuclear export. Finally, nuclear export of the NES reporter protein was significantly inhibited in cells in which nuclear export of mRNAs had been specifically blocked by microinjection of anti-TAP antibodies or by expression of a dominant negative form of NUP160. These results demonstrate a novel role for ongoing synthesis and export of mRNAs in NES-dependent protein nuclear export.
Heather M O'Hagan; Mats Ljungman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Experimental cell research     Volume:  297     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-06-23     Completed Date:  2004-08-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  548-59     Citation Subset:  IM    
Department of Radiation Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, USA.
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MeSH Terms
ATP-Binding Cassette Transporters
Active Transport, Cell Nucleus / drug effects*
Cell Nucleus / drug effects,  metabolism*
Cells, Cultured
Cytoplasm / drug effects,  metabolism
Dose-Response Relationship, Drug
Fibroblasts / cytology,  metabolism
Fluorescent Dyes
Glutathione Transferase / metabolism
Green Fluorescent Proteins
Histocompatibility Antigens Class I / metabolism
Karyopherins / metabolism
Luminescent Proteins
Models, Biological
Nuclear Localization Signals / metabolism*
Nuclear Pore Complex Proteins / metabolism
Nuclear Proteins / metabolism
RNA, Messenger / antagonists & inhibitors,  biosynthesis*,  drug effects,  metabolism*
Receptors, Cytoplasmic and Nuclear*
Recombinant Proteins / metabolism
Ribonuclease, Pancreatic / pharmacology
Transcription, Genetic / drug effects
Grant Support
Reg. No./Substance:
0/ATP-Binding Cassette Transporters; 0/Fluorescent Dyes; 0/Histocompatibility Antigens Class I; 0/Karyopherins; 0/Luminescent Proteins; 0/NUP160 protein, human; 0/Nuclear Localization Signals; 0/Nuclear Pore Complex Proteins; 0/Nuclear Proteins; 0/RNA, Messenger; 0/Receptors, Cytoplasmic and Nuclear; 0/Recombinant Proteins; 0/Rhodamines; 0/exportin 1 protein; 0/transporter associated with antigen processing (TAP); 147336-22-9/Green Fluorescent Proteins; EC Transferase; EC, Pancreatic

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