Architecture of RNA-RNA interactions.

RNA molecules tend to form intricate tertiary structures via intramolecular RNA-RNA interactions (RRIs) to regulate transcription, RNA processing, and translation processes. In these biological processes, RNAs, especially noncoding RNAs, usually achieve their regulatory specificity through intermolecular RNA-RNA base pairing and execute their regulatory outcomes via associated RNA-binding proteins. Decoding intramolecular and intermolecular RRIs is a prerequisite for understanding the architecture of various RNA molecules and their regulatory roles in development, differentiation, and disease. Many sequencing-based methods have recently been invented and have revealed extraordinarily complicated RRIs in mammalian cells. Here, we discuss the technical advances and limitations of various methodologies developed for studying cellular RRIs, with a focus on the emerging architectural roles of RRIs in gene regulation.