Structure of PTB Bound to RNA: Specific Binding and Implications for Splicing Regulation

The polypyrimidine tract binding protein (PTB) is a 58-kDa RNA binding protein involved in multiple aspects of mRNA metab., including the repression of alternative exons. We have detd. the soln. structures of the four RNA binding domains (RBDs) of PTB, each bound to a CUCUCU oligonucleotide. Each RBD binds RNA with a different binding specificity. RBD3 and RBD4 interact, resulting in an antiparallel orientation of their bound RNAs. Thus, PTB will induce RNA looping when bound to two sepd. pyrimidine tracts within the same RNA. This leads to structural models for how PTB functions as an alternative-splicing repressor. [on SciFinder (R)]