Drug discovery with an RBM20 dependent titin splice reporter identifies cardenolides as lead structures to improve cardiac filling
Fig 7
Digitoxin alters transcription of splicing related genes.
(a) Stepwise assembly of major spliceosomal small nuclear ribonucleo proteins (snRNPs) on pre-mRNA. The removal of non-coding sequence from pre-mature mRNA transcripts requires five RNP complexes U1, U2, U4, U5 and U6. Boxes display the genes related to RNA unwinding and complex remodelling/recycling (DExD/H box proteins) as well as factors necessary for the transesterification. 9 of 12 genes are significantly downregulated by at least 20%. Boxes with thick outlines represent proteins binding RBM20 [22]. (b) Target specific factors from human spliceosomal complexes A, B, Bact and C that are dynamically integrated into active spliceosomes. Almost half of the genes in RBM20 dependent splicing complexes are significantly regulated by digitoxin.