title: FXR1P but not FMRP regulates the levels of mammalian brain-specific microRNA-9 and microRNA-124.
abstract: Mammalian brain-specific miR-9 and miR-124 have been implicated in several aspects of neuronal development and function. However, it is not known how their expression levels are regulated in vivo. We found that the levels of miR-9 and miR-124 are regulated by FXR1P but not by the loss of FXR2P or FMRP in vivo, a mouse model of fragile X syndrome. Surprisingly, the levels of miR-9 and miR-124 are elevated in fmr1/fxr2 double-knock-out mice, in part reflecting posttranscriptional upregulation of FXR1P. Indeed, FXR1P is required for efficient processing of pre-miR-9 and pre-miR-124 in vitro and forms a complex with Dicer and pre-miRNAs. These findings reveal differential roles of FMRP family proteins in controlling the expression levels of brain-specific miRNAs.
authors.affiliation: Gladstone Institute of Neurological Disease, San Francisco, California 94158, USA.
authors.forename: Xia-Lian
authors.initials: XL
authors.lastname: Xu
authors.forename: Ruiting
authors.initials: R
authors.lastname: Zong
authors.forename: Zhaodong
authors.initials: Z
authors.lastname: Li
authors.forename: Md Helal Uddin
authors.initials: MH
authors.lastname: Biswas
authors.forename: Zhe
authors.initials: Z
authors.lastname: Fang
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.forename: Fen-Biao
authors.initials: FB
authors.lastname: Gao
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology; D005600:Fragile X Syndrome / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: D053487:DEAD-box RNA Helicases; D051860:Fragile X Messenger Ribonucleoprotein 1; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D043244:Ribonuclease III; C096916:FXR1 protein, human; C497684:Fmr1 protein, mouse; C551804:MIRN9 microRNA, mouse; C540079:Mirn124 microRNA, mouse; C509781:Dicer1 protein, mouse