CRM1-dependent function of a cis-acting RNA export element.
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.
Popa
Ileana
I
Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Harris
Matthew E
ME
Donello
John E
JE
Hope
Thomas J
TJ
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D017930:Genes, Reporter; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics*; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014764:Viral Proteins / Q000378:metabolism; D000097606:Exportin 1 Protein
D005231:Fatty Acids, Unsaturated; D028884:Karyopherins; D028861:Nuclear Pore Complex Proteins; D012367:RNA, Viral; D018160:Receptors, Cytoplasmic and Nuclear; D014764:Viral Proteins; D000097606:Exportin 1 Protein; C085914:NUP214 protein, human; C038753:leptomycin B