RNA G-quadruplexes: emerging mechanisms in disease

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• RNA G-quadruplexes (G4s) are four-stranded structures formed by G-rich RNA sequences.
• These structures are implicated in diverse cellular functions, including DNA processes and RNA post-transcriptional regulation.
• Aberrant regulation of RNA G4s is associated with numerous human diseases.

Purpose of the Study:

• To review the molecular mechanisms linking RNA G4s to human diseases.
• To present models of RNA G4 deregulation in disease pathogenesis.
• To survey functional RNA G4s and their mechanisms of action.

Main Methods:

• Literature review of experimental studies and bioinformatic predictions.
• Analysis of proposed molecular mechanisms of RNA G4 deregulation.
• Comprehensive survey of functional RNA G4s.

Main Results:

• RNA G4s are involved in transcription, translation, and RNA processing.
• Disease-associated mechanisms include protein sequestration, aberrant protein expression/localization, RAN translation, translational blockade, and disruption of protein-G4 complexes.
• Several overlapping models of RNA G4 deregulation in disease are proposed.

Conclusions:

• RNA G4s play critical roles in cellular functions and human health.
• Understanding RNA G4 deregulation mechanisms is key to addressing associated diseases.
• Further research is needed to elucidate RNA G4-mediated regulatory mechanisms in disease.