RNA sequencing of control and myotonic dystrophy type 1 fibroblasts with SNRPD2 knockdown
Myotonic dystrophy type 1 or DM1 is an autosomal dominant genetic disorder caused by excessive CTG repeats in the DMPK gene. In addition to DM1 being a common adult-onset muscular dystrophy, it can affect tissues in organs including the brain, eyes, and heart. Post-transcriptionally the CUG repeats in the 3 prime UTR of the DMPK transcripts form a secondary structure and readily the bind muscleblind-like (MBNL) family of alternative splicing regulators. MBNL bound to CUG repeats cannot simultaneously serve the role of an alternative splicing factor, and as a result, this sequestration leads to the global mis-splicing of pre-mRNA transcripts, which leads to many of the disease phenotypes. Small nuclear ribonucleoprotein D2 or SNRPD2 is a core component of the spliceosome needed for pre-mRNA splicing. The purpose of the study is to determine if modulation of splicing factors levels, particularly SNRPD2, can rescue alternative splicing phenotypes in DM1 model systems.