title: CUGBP1 and MBNL1 preferentially bind to 3' UTRs and facilitate mRNA decay.
abstract: CUGBP1 and MBNL1 are developmentally regulated RNA-binding proteins that are causally associated with myotonic dystrophy type 1. We globally determined the in vivo RNA-binding sites of CUGBP1 and MBNL1. Interestingly, CUGBP1 and MBNL1 are both preferentially bound to 39 UTRs. Analysis of CUGBP1- and MBNL1-bound 39 UTRs demonstrated that both factors mediate accelerated mRNA decay and temporal profiles of expression arrays supported this. Role of CUGBP1 on accelerated mRNA decay has been previously reported, but the similar function of MBNL1 has not been reported to date. It is well established that CUGBP1 and MBNL1 regulate alternative splicing. Screening by exon array and validation by RT-PCR revealed position dependence of CUGBP1- and MBNL1-binding sites on the resulting alternative splicing pattern. This study suggests that regulation of CUGBP1 and MBNL1 is essential for accurate control of destabilization of a broad spectrum of mRNAs as well as of alternative splicing events.
authors.affiliation: Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Masuda
authors.forename: Henriette Skovgaard
authors.initials: HS
authors.lastname: Andersen
authors.forename: Thomas Koed
authors.initials: TK
authors.lastname: Doktor
authors.forename: Takaaki
authors.initials: T
authors.lastname: Okamoto
authors.forename: Mikako
authors.initials: M
authors.lastname: Ito
authors.forename: Brage Storstein
authors.initials: BS
authors.lastname: Andresen
authors.forename: Kinji
authors.initials: K
authors.lastname: Ohno
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D001483:Base Sequence; D000067879:CELF1 Protein; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D000067879:CELF1 Protein; C102843:CELF1 protein, human; D017931:DNA Primers; C493663:MBNL1 protein, human; D016601:RNA-Binding Proteins