RNA G-quadruplex structures control ribosomal protein production

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Four-stranded guanine-quadruplex (G4) structures are known to form from guanine-rich sequences.
• Their prevalence and function in cellular RNA remain largely uncharacterized.

Purpose of the Study:

• To investigate the presence and role of endogenous RNA G4s in the human transcriptome.
• To explore the impact of RNA G4s on protein translation, particularly for ribosomal proteins.

Main Methods:

• Utilized G4-interacting protein binding sites (DDX3X, DHX36, GRSF1) to identify potential RNA G4s.
• Employed the BG4 antibody to detect folded RNA G4s in cross-linked cellular lysates.
• Assessed the effect of G4 disruption and helicase depletion on translation in vitro and in cells.

Main Results:

• Identified endogenous RNA G4s in the human cytoplasmic transcriptome, enriched in 5' UTRs of ribosomal protein mRNAs.
• Demonstrated that disruption of these G4s impairs ribosomal protein translation in vitro.
• Showed that inhibiting G4-resolving helicases or stabilizing G4s affects ribosomal protein mRNA translation in cells.

Conclusions:

• RNA G4s are prevalent in the human transcriptome and play a significant role in regulating protein translation.
• These structures offer a common mechanism for translational co-regulation, with implications for diseases involving translation dysregulation, such as cancer.