How stop codon pseudouridylation induces nonsense suppression
Document Type
Article
Publication Date
10-1-2021
Abstract
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.
Keywords
Pseudouridylation, Nonsense suppression, Ribosome, Density functional theory
Divisions
CHEMISTRY,PHYSICS
Publication Title
Computational and Theoretical Chemistry
Volume
1204
Publisher
Elsevier
Publisher Location
RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS