MicroRNAs (miRNAs) are a class of small, noncoding RNAs that function by regulating gene expression post-transcriptionally. Alterations in miRNA expression can strongly influence cellular physiology. Here we demonstrated cross-regulation between two components of the RNA interference (RNAi) machinery in human cells. Inhibition of exportin-5, the karyopherin responsible for pre-miRNA export, downregulated expression of Dicer, the RNase III required for pre-miRNA maturation. This effect was post-transcriptional and resulted from an increased nuclear localization of Dicer mRNA. In vitro assays and cellular RNA immunoprecipitation experiments showed that exportin-5 interacted directly with Dicer mRNA. Titration of exportin-5 by overexpression of either pre-miRNA or the adenoviral VA1 RNA resulted in loss of Dicer mRNA-exportin-5 interaction and reduction of Dicer level. This saturation also occurred during adenoviral infection and enhanced viral replication. Our study reveals an important cross-regulatory mechanism between pre-miRNA or viral small RNAs and Dicer through exportin-5.
Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels
Bennasser, Y.; Chable-Bessia, C.; Triboulet, R.; Gibbings, D.; Gwizdek, C.; Dargemont, C.; Kremer, E. J.; Voinnet, O.; Benkirane, M.
Nat Struct Mol Biol
2011-03 / vol 18 / pages 323-7
nsmb.1987 [pii] 10.1038/nsmb.1987
1545-9985 (Electronic) 1545-9985 (Linking)
IGMM team(s) involved in this publication
Eric J Kremer
Adenovirus: receptors, trafficking, immunogenicity & vectorology
Humans; *Gene Expression Regulation; Virus Replication; Protein Binding; RNA Interference; RNA, Messenger/genetics/*metabolism; RNA, Viral/genetics/*metabolism; Adenoviridae Infections/virology; Adenoviridae/genetics/physiology; DEAD-box RNA Helicases/*genetics/metabolism; Hela Cells; Karyopherins/genetics/*metabolism; MicroRNAs/genetics/*metabolism; Ribonuclease III/*genetics/metabolism