RNA–Protein Interactions

In this chapter, the chemical principles that underlie protein–RNA interactions are examined and the fundamental mechanisms by which proteins associate with specific targets in RNA molecules are identified. Although RNA binding proteins (RBPs) are similar to DNA binding proteins in terms of the variety of non-covalent interactions that dominate the nucleic acid–protein interface, the great variety of complex structures of RNAs necessarily results in a greater diversity and complexity in the structure of RBPs and, therefore, in the mechanisms of their binding. Modular structures of RBPs embrace one or more RNA binding domains (RBDs). In addition, there are multiple classes of RBDs, each with their own characteristic conserved amino acid sequence and folded structure. The biological functions of RBPs demand specificity in binding their target, which is a target for ongoing exploration. Looking ahead, it has been optimistically recognized that selection of binding sites within the ‘sea’ of structurally similar alternative binding sites in the transcriptome presents a significant and persistent challenge for future discoveries. Moreover, RBPs are associated with human diseases and understanding of the structure and function of RBPs has advanced to the stage that they can realistically be identified as targets for therapeutic chemicals.