How stop codon pseudouridylation induces nonsense suppression

• Main Authors: Monajemi, Hadieh, Zain, Sharifuddin M.
• Format: Article
• Published: Elsevier 2021
• Subjects: QC Physics; QD Chemistry
• Online Access: http://eprints.um.edu.my/26901/

Nonsense mutation can be an inherited disorder or caused by genetic mutation under certain conditions such as stress or exposure. Nonsense suppression, can have a broad potential as a therapeutic approach to nonsense mutation. Pseudouridine is proposed to result in nonsense suppression if induced in one of the three nonsense codons, Amber, Ochre, or Opal. Understanding how pseudouridine in stop codon induces nonsense suppression is vital for preventing nonsense mutation. Using in-silico analysis with DFT, we have simulated different near and non-cognate codon-anticodon interactions with pseudouridylated and normal nonsense codons. The structural analysis show that pseudouridylation of the nonsense codons in the first position leads to the mRNA-tRNA helix major groove conformation and formation of unusual Hoogsteen base pair in the purine bases at the second or third position. This leads to stabilized base-pair interaction and pi...pi stacking for the pseudouridylated nonsense codon compared its normal nonsense codon counterpart.