Idiosyncratic recognition of UUG/UUA codons by modified nucleoside 5-taurinomethyluridine, [tau]m.sup.5U present at 'wobble' position in anticodon loop of tRNA.sup.Leu: A molecular modeling approach

Lack of naturally occurring modified nucleoside 5-taurinomethyluridine ([tau]m.sup.5 U) at the 'wobble' 34.sup.th position in tRNA.sup.Leu causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The [tau]m.sup.5 U.sub.34 specifically recognizes UUG and UUA codons. Structural consequences of [tau]m.sup.5 U.sub.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.sup.Leu in presence and absence of [tau]m.sup.5 U.sub.34 along with UUG and UUA codons were performed to explore the dynamic behaviour of [tau]m.sup.5 U.sub.34 during codon recognition process. The MD simulation results revealed that [tau]m.sup.5 U.sub.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 [tau]m.sup.5 U.sub.34 modification over the other models, lacking [tau]m.sup.5 U.sub.34 . Another MD simulation study of 55S mammalian mitochondrial rRNA with tRNA.sup.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.sup.Leu with [tau]m.sup.5 U.sub.34 to recognize UUG and UUA codons.