title: Alternative splicing of myomesin 1 gene is aberrantly regulated in myotonic dystrophy type 1.
abstract: Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by a CTG repeat expansion in the 3'-UTR of dystrophia myotonica-protein kinase. Aberrant regulation of alternative splicing is a characteristic feature of DM. Dozens of genes have been found to be abnormally spliced; however, few reported splicing abnormalities explain the phenotypes of DM1 patients. Thus, we hypothesized that other, unknown abnormal splicing events exist. Here, by using exon array, we identified aberrant inclusion of myomesin 1 (MYOM1) exon 17a as a novel splicing abnormality in DM1 muscle. A cellular splicing assay with a MYOM1 minigene revealed that not only MBNL1-3 but also CELF1 and 2 decreased the inclusion of MYOM1 exon 17a in HEK293T cells. Expression of expanded CUG repeat impeded MBNL1 activity but did not affect CELF1 activity on the splicing of MYOM1 minigene. Our results suggest that the downregulation of MBNL proteins should lead to the abnormal splicing of MYOM1 exon 17a in DM1 muscle.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Japan.
authors.forename: Michinori
authors.initials: M
authors.lastname: Koebis
authors.forename: Natsumi
authors.initials: N
authors.lastname: Ohsawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kino
authors.forename: Noboru
authors.initials: N
authors.lastname: Sasagawa
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ishiura
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D000067879:CELF1 Protein; D064211:Connectin; D016384:Consensus Sequence; D005091:Exons; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D009223:Myotonic Dystrophy / Q000235:genetics* / Q000378:metabolism; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins / Q000378:metabolism
chemical_list: D000067879:CELF1 Protein; C102843:CELF1 protein, human; D064211:Connectin; C493663:MBNL1 protein, human; C577299:MYOM1 protein, human; D009124:Muscle Proteins; D022821:RNA Splice Sites; D016601:RNA-Binding Proteins