G-quadruplexes from non-coding RNAs

Non-coding RNAs (ncRNAs) are significant regulators of gene expression in a wide range of biological processes, such as transcription, RNA maturation, or translation. ncRNAs interplay with proteins or other RNAs through not only classical sequence-based mechanisms but also unique higher-order structures such as RNA G-quadruplexes (rG4s). rG4s are predictably formed in guanine-rich sequences and are closely related to various human diseases, such as tumors, neurodegenerative diseases, and infections. This review focuses on the vital role of rG4s in ncRNAs, particularly lncRNAs and miRNAs. We outline the dynamic balance between rG4s and RNA stem-loop/hairpin structures and the interplay between ncRNAs and interactors, thereby modulating gene expression and disease progression. A complete understanding of the biological regulatory role and mechanism of rG4s in ncRNAs affirms the critical importance of folding into the appropriate three-dimensional structure in maintaining or modulating the functions of ncRNAs. It makes them novel therapeutic targets for adjusting potential-G4-containing-ncRNAs-associated diseases.