title: Competition for XPO5 binding between Dicer mRNA, pre-miRNA and viral RNA regulates human Dicer levels.
abstract: 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.
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Génétique Humaine UPR1142, Montpellier, France.
authors.forename: Yamina
authors.initials: Y
authors.lastname: Bennasser
authors.forename: Christine
authors.initials: C
authors.lastname: Chable-Bessia
authors.forename: Robinson
authors.initials: R
authors.lastname: Triboulet
authors.forename: Derrick
authors.initials: D
authors.lastname: Gibbings
authors.forename: Carole
authors.initials: C
authors.lastname: Gwizdek
authors.forename: Catherine
authors.initials: C
authors.lastname: Dargemont
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Kremer
authors.forename: Olivier
authors.initials: O
authors.lastname: Voinnet
authors.forename: Monsef
authors.initials: M
authors.lastname: Benkirane
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000257:Adenoviridae Infections / Q000821:virology; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D028884:Karyopherins; D035683:MicroRNAs; D012333:RNA, Messenger; D012367:RNA, Viral; C446511:XPO5 protein, human; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases