title: Post-transcriptional regulation of fukutin in an astrocytoma cell line.
abstract: Fukutin is the gene responsible for Fukuyama-type congenital muscular dystrophy (FCMD), an autosomal recessive disease associated with central nervous system (CNS) and eye anomalies. Fukutin is involved in basement membrane formation via the glycosylation of α-dystroglycan (α-DG), and hypoglycosylation of α-DG provokes the muscular, CNS and eye lesions of FCMD. Astrocytes play an important role in the pathogenesis of the CNS lesions, but the post-transcriptional regulation of fukutin mRNA has not been elucidated. In this study, we investigated the characteristics of fukutin mRNA using an astrocytoma cell line that expresses fukutin and glycosylated α-DG. The glycosylation of α-DG was considered to be increased by over-expression of fukutin and decreased by knockdown of fukutin. Knockdown of Musashi-1, one of the RNA-binding proteins involved in the regulation of neuronal differentiation, induced a decrease in fukutin mRNA. Immunoprecipitation and ELISA-based RNA-binding assay demonstrated possible binding between fukutin mRNA and Musashi-1 protein. A relationship between fukutin mRNA and vimentin protein was also proposed. In situ hybridization for fukutin mRNA showed a positive cytoplasmic reaction including cytoplasmic processes. From these results, fukutin mRNA is suggested to be a localized mRNA up-regulated by Musashi-1 and to be a component of a mRNA-protein complex which includes Musashi-1 and (presumably) vimentin proteins.
authors.affiliation: Department of Pathology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan. sheto@research.twmu.ac.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Atsuko
authors.initials: A
authors.lastname: Hiroi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Shibata
authors.forename: Makiko
authors.initials: M
authors.lastname: Osawa
authors.forename: Makio
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D049030:Dystroglycans / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D058494:Walker-Warburg Syndrome / Q000235:genetics
chemical_list: C113587:FKTN protein, human; D007797:Laminin; C491297:MSI1 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D049030:Dystroglycans