Poly-guanine RNAs form ultra-stable intermolecular G-quadruplexes to suppress RNA function at low environmental temperature

Intramolecular G-quadruplexes (G4) are four-stranded nucleic acid structures formed by guanine-rich sequences that play crucial roles in various biological processes, such as gene regulation and genome stability. However, the formation and function of intermolecular G4, especially in RNA, remain less understood. In this study, it was demonstrated that poly-guanine (poly-G) RNA sequences can form ultra-stable intermolecular G4 structures, particularly when the guanine content exceeds five. The stability and formation of RNA intermolecular G4 were further investigated under various physicochemical conditions, with temperature identified as a critical influencing factor. Furthermore, stable intermolecular G4 was shown to significantly inhibit RNA reverse transcription, and poly-G miRNAs were found to form stable G4 with poly-G mRNAs. Further analysis revealed a significant correlation between guanine content and environmental temperature, based on nucleic acid sequence analysis across organisms with different environmental temperatures and evolutionary simulations involving bacterial resistance genes. We proposed that the formation of intermolecular G4 to inhibit RNA function is a potential molecular mechanism by which genetic material responds to changes in the organism's environmental temperature. This study enhances our understanding of RNA G4 biology and suggests that poly-G sequences may play a critical role in the molecular response of organisms to environmental temperature fluctuations, offering new insights into the adaptation mechanisms of genetic material to climate and environmental changes.