How stop codon pseudouridylation induces nonsense suppression

Monajemi, Hadieh and Zain, Sharifuddin M. (2021) How stop codon pseudouridylation induces nonsense suppression. Computational and Theoretical Chemistry, 1204. ISSN 2210-271X, DOI

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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.

Item Type: Article
Uncontrolled Keywords: Pseudouridylation; Nonsense suppression; Ribosome; Density functional theory
Subjects: Q Science > QC Physics
Q Science > QD Chemistry
Divisions: Faculty of Science > Department of Chemistry
Faculty of Science > Department of Physics
Depositing User: Ms Zaharah Ramly
Date Deposited: 20 Apr 2022 07:43
Last Modified: 20 Apr 2022 07:43

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