Pervasive transcription of the human genome generates a massive amount of noncoding RNAs (ncRNAs) that lack protein-coding potential but play crucial roles in development, differentiation, and tumorigenesis. To achieve these biological functions, ncRNAs must first fold into intricate structures via intramolecular RNA-RNA interactions (RRIs) and then interact with different RNA substrates via intermolecular RRIs. RRIs are usually facilitated, stabilized, or mediated by RNA-binding proteins. With this guiding principle, several protein-based high-throughput methods have been developed for unbiased mapping of defined or all RNA-binding protein-mediated RRIs in various species and cell lines. In addition, some chemical-based approaches are also powerful to detect RRIs globally based on the fact that RNA duplex can be cross-linked by psoralen or its derivative 4'-aminomethyltrioxsalen. These efforts have significantly expanded our understanding of RRIs in determining the specificity and variability of gene regulation. Here, we review the current knowledge of the regulatory roles of RRI, focusing on their emerging roles in transcriptional regulation and nuclear body formation. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry.
Keywords: RNA-RNA interactions; RNA-binding protein; phase separation; structure; transcription.
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