Decoding protein–RNA interactions using CLIP-based methodologies

Protein–RNA interactions are central to all RNA processing events, with pivotal roles in the regulation of gene expression and cellular functions. Dysregulation of these interactions has been increasingly linked to the pathogenesis of human diseases. High-throughput approaches to identify RNA-binding proteins and their binding sites on RNA — in particular, ultraviolet crosslinking followed by immunoprecipitation (CLIP) — have helped to map the RNA interactome, yielding transcriptome-wide protein–RNA atlases that have contributed to key mechanistic insights into gene expression and gene-regulatory networks. Here, we review these recent advances, explore the effects of cellular context on RNA binding, and discuss how these insights are shaping our understanding of cellular biology. We also review the potential therapeutic applications arising from new knowledge of protein–RNA interactions.