Molecular basis of titin exon exclusion by RBM20 and the novel titin splice regulator PTB4.

ABSTRACT: RNA-binding motif protein 20 (RBM20) is a cardiac splice regulator that adapts cardiac filling via its diverse substrates-including the sarcomeric protein titin. The molecular basis and regulation of RBM20-dependent exon exclusion are largely unknown. In tissue culture experiments, we show that the combination of RNA recognition motif (RRM) and C-terminus is necessary and sufficient for RBM20 activity, indicating an important function of the ZnF2 domain in splicing repression. Using splice reporter and in vitro binding assays targeting titin exons 241-243, we identified a minimal genomic segment that is necessary for RBM20-mediated splicing repression of the alternative exon. Here, RBM20 binds the cluster containing most RBM20 binding motifs through its RRM domain and represses the upstrea

SUBMITTER: Dauksaite V 

PROVIDER: S-EPMC6007684 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature