Idiosyncratic recognition of UUG/UUA codons by modified nucleoside 5-taurinomethyluridine, τm(5)U present at ‘wobble’ position in anticodon loop of tRNA(Leu): A molecular modeling approach

Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (τm(5)U) at the ‘wobble’ 34(th) position in tRNA(Leu) causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The τm(5)U(34) specifically recognizes UUG and UUA codons. Structural consequences of τm(5)U(34) to read cognate codons have not been studied so far in detail at the atomic level. Hence, 50ns multiple molecular dynamics (MD) simulations of various anticodon stem loop (ASL) models of tRNA(Leu) in presence and absence of τm(5)U(34) along with UUG and UUA codons were performed to explore the dynamic behaviour of τm(5)U(34) during codon recognition process. The MD simulation results revealed that τm(5)U(34) recognizes G/A ending codons by ‘wobble’ as well as a novel ‘single’ hydrogen bonding interactions. RMSD and RMSF values indicate the comparative stability of the ASL models containing τm(5)U(34) modification over the other models, lacking τm(5)U(34). Another MD simulation study of 55S mammalian mitochondrial rRNA with tRNA(Leu) showed crucial interactions between the A-site residues, A918, A919, G256 and codon-anticodon bases. Thus, these results could improve our understanding about the decoding efficiency of human mt tRNA(Leu) with τm(5)U(34) to recognize UUG and UUA codons.