Key result
Aberrant inclusion of myomesin 1 (MYOM1) exon 17a was identified as a novel splicing abnormality in DM1 muscle, likely driven by the downregulation of MBNL proteins.
Identifies aberrant inclusion of MYOM1 exon 17a as a novel splicing abnormality in DM1 muscle driven by MBNL protein downregulation.
Answers are grounded in this paper and cite their sources.
New DM1 splicing target may link to phenotypes; leaves open functional role and need for validation studies.
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.
No takes yet. Share an insight, caveat, or question.
Koebis et al. (2011) studied Myotonic dystrophy type 1 (DM1). Expanded CUG repeat expression was evaluated on Inclusion of myomesin 1 (MYOM1) exon 17a. Aberrant inclusion of myomesin 1 (MYOM1) exon 17a was identified as a novel splicing abnormality in DM1 muscle, likely driven by the downregulation of MBNL proteins.
Synapse has enriched 10 related papers. Consider them for comparative context: