title: Exportin-5 orthologues are functionally divergent among species.
abstract: Exportin-5, an evolutionarily conserved nuclear export factor belonging to the importin-beta family of proteins, is known to play a role in the nuclear export of small noncoding RNAs such as precursors of microRNA, viral minihelix RNA and a subset of tRNAs in mammalian cells. In this study, we show that the exportin-5 orthologues from different species such as human, fruit fly and yeast exhibit diverged functions. We found that Msn5p, a yeast exportin-5 orthologue, binds double-stranded RNAs and that it prefers a shorter 22 nt, double-stranded RNA to approximately 80 nt pre-miRNA, even though both of these RNAs share a similar terminal structure. Furthermore, we found that Drosophila exportin-5 binds pre-miRNAs and that amongst the exportin-5 orthologues tested, it shows the highest affinity for tRNAs. The knockdown of Drosophila exportin-5 in cultured cells decreased the amounts of tRNA as well as miRNA, whereas the knock down of human exportin-5 in cultured cells affected only miRNA but not tRNA levels. These results indicate that double-stranded RNA binding ability is an inherited functional characteristic of the exportin-5 orthologues and that Drosophila exportin-5 functions as an exporter of tRNAs as well as pre-miRNAs in the fruit fly that lacks the orthologous gene for exportin-t.
authors.affiliation: Department of Cell Biology and Neuroscience, Graduate School of Medicine, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shibata
authors.forename: Mitsuho
authors.initials: M
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Miki
authors.forename: Akira
authors.initials: A
authors.lastname: Shimamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Jun
authors.initials: J
authors.lastname: Katahira
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoneda
mesh_terms: D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000166:cytology; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D028884:Karyopherins / Q000378:metabolism* / Q000502:physiology; D035683:MicroRNAs / Q000378:metabolism; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D028884:Karyopherins; C401306:MSN5 protein, S cerevisiae; D035683:MicroRNAs; D012330:RNA, Double-Stranded; C514587:RanBP21 protein, Drosophila; D029701:Saccharomyces cerevisiae Proteins; C446511:XPO5 protein, human; D012343:RNA, Transfer