From parts lists to functional significance—RNA–protein interactions in gene regulation

Hundreds of canonical RNA binding proteins facilitate diverse and essential RNA processing steps in cells forming a central regulatory point in gene expression. However, recent discoveries including the identification of a large number of noncanonical proteins bound to RNA have changed our view on RNA–protein interactions merely as necessary steps in RNA biogenesis. As the list of proteins interacting with RNA has expanded, so has the scope of regulation through RNA–protein interactions. In addition to facilitating RNA metabolism, RNA binding proteins help to form subcellular structures and membraneless organelles, and provide means to recruit components of macromolecular complexes to their sites of action. Moreover, RNA–protein interactions are not static in cells but the ribonucleoprotein (RNP) complexes are highly dynamic in response to cellular cues. The identification of novel proteins in complex with RNA and ways cells use these interactions to control cellular functions continues to broaden the scope of RNA regulation in cells and the current challenge is to move from cataloguing the components of RNPs into assigning them functions. This will not only facilitate our understanding of cellular homeostasis but may bring in key insights into human disease conditions where RNP components play a central role. This review brings together the classical view of regulation accomplished through RNA–protein interactions with the novel insights gained from the identification of RNA binding interactomes. We discuss the challenges in combining molecular mechanism with cellular functions on the journey towards a comprehensive understanding of the regulatory functions of RNA–protein interactions in cells. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications aRNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes RNA Interactions with Proteins and Other Molecules > Protein–RNA Recognition.