Idiosyncratic recognition of UUG/UUA codons by modified nucleoside 5-taurinomethyluridine, τm5U present at ‘wobble’ position in anticodon loop of tRNALeu: A molecular modeling approach

by Asmita S. Kamble, Prayagraj M. Fandilolu, Susmit B. Sambhare, Kailas D. Sonawane

Lack of naturally occurring modified nucleoside 5-taurinomethyluridine (τm⁵U) at the ‘wobble’ 34^th position in tRNA^Leu causes mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). The τm⁵U₃₄ specifically recognizes UUG and UUA codons. Structural consequences of τm⁵U₃₄ 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 τm⁵U₃₄ along with UUG and UUA codons were performed to explore the dynamic behaviour of τm⁵U₃₄ during codon recognition process. The MD simulation results revealed that τm⁵U₃₄ 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 τm⁵U₃₄ modification over the other models, lacking τm⁵U₃₄. 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 τm⁵U₃₄ to recognize UUG and UUA codons.

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