THE REGULATION OF ALTERNATIVE SPLICING ASSOCIATED WITH MYOTONIC DYSTROPHY by MICHAEL BRYAN WARP A DISSERTATION
نویسندگان
چکیده
منابع مشابه
Colocalization of muscleblind with RNA foci is separable from mis-regulation of alternative splicing in myotonic dystrophy.
Myotonic dystrophy type I (DM1), which is caused by a non-coding CTG-repeat expansion in the dystrophia myotonica-protein kinase (DMPK) gene, is an RNA-mediated disease. Expanded CUG repeats in transcripts of mutant DMPK form nuclear foci that recruit muscleblind-like (MBNL) proteins, a family of alternative splicing factors. Although transcripts of mutant DMPK and MBNL proteins accumulate in n...
متن کاملNuclear RNA foci in the heart in myotonic dystrophy.
The disease mechanism underlying myotonic dystrophy type 1 (DM1) pathogenesis in skeletal muscle may involve sequestration of RNA binding proteins in nuclear foci of expanded poly(CUG) RNA. Here we report evidence for a parallel mechanism in the heart. Accumulation of expanded poly(CUG) RNA in nuclear foci is associated with sequestration of muscleblind proteins and abnormal regulation of alter...
متن کاملCongenital myotonic dystrophy-an RNA-mediated disease across a developmental continuum.
Thomas and colleagues (pp. 1122-1133) demonstrate severe dysregulation of developmentally regulated alternative splicing and polyadenylation in congenital myotonic dystrophy (CDM). In doing so, they also highlight the importance of these post-transcriptional processes during normal fetal muscle development. Finally, they generate and characterize a mouse model of CDM that lacks all three Muscle...
متن کاملDose-Dependent Regulation of Alternative Splicing by MBNL Proteins Reveals Biomarkers for Myotonic Dystrophy
Alternative splicing is a regulated process that results in expression of specific mRNA and protein isoforms. Alternative splicing factors determine the relative abundance of each isoform. Here we focus on MBNL1, a splicing factor misregulated in the disease myotonic dystrophy. By altering the concentration of MBNL1 in cells across a broad dynamic range, we show that different splicing events r...
متن کاملPentamidine reverses the splicing defects associated with myotonic dystrophy.
Myotonic dystrophy (DM) is a genetic disorder caused by the expression (as RNA) of expanded CTG or CCTG repeats. The alternative splicing factor MBNL1 is sequestered to the expanded RNA repeats, resulting in missplicing of a subset of pre-mRNAs linked to symptoms found in DM patients. Current data suggest that if MBNL1 is released from sequestration, disease symptoms may be alleviated. We ident...
متن کامل