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Molecular and Cellular Biology, April 2002, p. 2057-2067, Vol. 22, No. 7
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.7.2057-2067.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

CRM1-Dependent Function of a cis-Acting RNA Export Element

Ileana Popa,1,2 Matthew E. Harris,2,{dagger} John E. Donello,2,{ddagger} and Thomas J. Hope1*

Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612,1 Graduate Programs in Molecular Pathology and Biology, University of California, San Diego, La Jolla, California 920372

Received 25 June 2001/ Returned for modification 19 July 2001/ Accepted 21 December 2001

Viruses often contain cis-acting RNA elements, which facilitate the posttranscriptional processing and export of their messages. These elements fall into two classes distinguished by the presence of either viral or cellular RNA binding proteins. To date, studies have indicated that the viral proteins utilize the CRM1-dependent export pathway, while the cellular factors generally function in a CRM1-independent manner. The cis-acting element found in the woodchuck hepatitis virus (WHV) (the WHV posttranscriptional regulatory element [WPRE]) has the ability to posttranscriptionally stimulate transgene expression and requires no viral proteins to function. Conventional wisdom suggests that the WPRE would function in a CRM1-independent manner. However, our studies on this element reveal that its efficient function is sensitive to the overexpression of the C terminus of CAN/Nup214 and treatment with the antimicrobial agent leptomycin B. Furthermore, the overexpression of CRM1 stimulates WPRE activity. These results suggest a direct role for CRM1 in the export function of the WPRE. This observation suggests that the WPRE is directing messages into a CRM1-dependent mRNA export pathway in somatic mammalian cells.


* Corresponding author. Mailing address: Department of Microbiology and Immunology (M/C 790), University of Illinois at Chicago College of Medicine, E-704 Medical Sciences Building, 835 S. Wolcott Ave., Chicago, IL 60612-7344. Phone: (312) 413-3424. Fax: (312) 996-6415. E-mail: thope{at}uic.edu.

{dagger} Present address: Walter Reed Army Institute of Research, Division of Retrovirology, Rockville, MD 20850.

{ddagger} Present address: Allergan, Inc., Irvine, CA 92623.


Molecular and Cellular Biology, April 2002, p. 2057-2067, Vol. 22, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.7.2057-2067.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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