RNA G-quadruplex in functional regulation of noncoding RNA: Challenges and emerging opportunities

G-quadruplexes (G4s) are stable, noncanonical structures formed in guanine (G)-rich sequences of DNA/RNA. G4 structures are reported to play a regulatory role in various cellular processes and, recently, a considerable number of studies have attributed new biological functions to these structures, especially in RNA. Noncoding RNA (ncRNA), which does not translate into a functional protein, is widely expressed and has been shown to play a key role in shaping cellular activity. There has been growing evidence of G4 formation in several ncRNA classes, and it has been identified as a key part for diverse biological functions and physio-pathological contexts in neurodegenerative diseases and cancer. This review discusses RNA G4s (rG4s) in ncRNA, focusing on the molecular mechanism underlying its function. This review also aims to highlight potential and emerging opportunities to identify and target the rG4s in ncRNA to understand its function and, ultimately, treat many diseases.