title: Expression of MBNL and CELF mRNA transcripts in muscles with myotonic dystrophy.
abstract: Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder that causes muscle wasting, myotonia, cardiac conduction abnormalities, and other multi-systemic symptoms. Current evidence supports a pathogenic mechanism involving aberrantly expanded CTG repeats in the 3'-untranslated region of the DM protein kinase (DMPK) gene. The repeats are thought to recruit various RNA-binding proteins such as muscleblind-like (MBNL) proteins into foci in the nuclei of DM cells, resulting in loss of function. However, aberrant regulation of transcription or subsequent RNA processing of MBNL-family mRNAs might also be part of the pathogenic mechanism of DM. We used real-time RT-PCR analysis to examine the possibility that MBNL mRNA expression is altered in DM1 patients. We also examined mRNA expression for members of the CUG-BP and ETR-3-like factor (CELF) family of RNA-binding proteins given that CELF proteins regulate alternative splicing and are also implicated in DM. We found that DM1 muscles displayed aberrant regulation of alternative splicing as reported previously; however, the levels of MBNL and CELF mRNA expression did not show any significant changes. Our results suggest that the expression and stability of the mRNA for these RNA-binding proteins are unaffected in DM1.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nezu
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: D000293:Adolescent; D000328:Adult; D000368:Aged; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009223:Myotonic Dystrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: C497252:CEBPD protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051743:CCAAT-Enhancer-Binding Protein-delta