Interplay between RNA-protein interactions and RNA structures in gene regulation

Cellular RNAs are not linear single-stranded stretches of nucleic acids as depicted in textbook cartoons but fold into secondary and tertiary structures through intra- and intermolecular base-pairing. They also interact with proteins to form ribonucleoproteins (RNPs), the functional units of RNA in cells. Recent methodological developments utilising high-throughput sequencing have enabled the detailed mapping of cellular RNA-protein interactions and RNA structures. While methods for the direct determination of cellular RNP structures are still lacking, the integration of high-throughput approaches and advancements with in vitro techniques such as cryogenic electron microscopy have provided insights into the functional significance of RNP structures. In this review, we will summarise the key methods used to probe cellular RNA-protein interactions and RNA structures and then provide examples of how these approaches have led to an enhanced understanding of RNP structures in gene regulation and how this has also opened new avenues for drug development.