Structural basis of UCUU RNA motif recognition by splicing factor RBM20

摘要: The vertebrate splicing factor RBM20 (RNA Binding Motif protein 20) regulates isoforms important for heart development and function, with mutations in the gene linked to cardiomyopathy. Previous studies have identified four base RNA motif UCUU as a common element pre-mRNA targeted by RBM20. Here, we determined structure of Recognition (RRM) domain from mouse bound containing sequence. atomic details show that RRM spans larger region than initially proposed order interact complete motif, well-folded C-terminal helix encoded exon 8 critical high affinity binding. This only forms upon binding final uracil, removing reduces well specificity. We therefore find uses coupled folding-binding mechanism specifically recognize motif.