4/2/2024 0 Comments Thirupugal govindarajan![]() ![]() Splicing in disease: disruption of the splicing code and the decoding machinery. RNA-binding proteins in human genetic disease. Lukong, K.E., Chang, K.-wei, Khandjian, E.W. SR proteins and related factors in alternative splicing. Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches. Our studies emphasize the key role of post-transcriptional regulation in cardiac function and provide mechanistic insights into the pathogenesis of human heart failure.Ĭhen, M. This network is enriched for genes that have previously been linked to cardiomyopathy, ion homeostasis and sarcomere biology. In addition to titin ( TTN), we identified a set of 30 genes with conserved splicing regulation between humans and rats. Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20-dependent regulation of alternative splicing. The phenotype of Rbm20-deficient rats resembled the pathology seen in individuals with dilated cardiomyopathy caused by RBM20 mutations. By positional cloning using a previously characterized rat strain with altered titin mRNA splicing, we identified a loss-of-function mutation in the gene encoding RNA binding motif protein 20 ( Rbm20) as the underlying cause of pathological titin isoform expression. Alternative splicing has a major role in cardiac adaptive responses, as exemplified by the isoform switch of the sarcomeric protein titin, which adjusts ventricular filling. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |