Nature maximizes the structural and functional diversities via chemically modification of the existing nucleic acid building blocks. Geranyl group is the most hydrophobic modification that having been recently identified on tRNA system in several bacteria1. Geranylated-tRNALysUU(ges2U) affected the protein translation level of E.coli by reducing the -1 frameshifting and the geranylation on tRNAGluCU(ges2U) increased the level of codon GAG recognition over GAA. To answer why geranyl group was selected to promote the xU-G pair over canonical xU-A pair, we have reported earlier that the base pairing specificity is effected by the length of the terpene chain which was functionalized at the sulfur position of 2-thiothymidine in the DNA-duplexes context. The relatively long chain length of ≥ C10 can stabilize the DNA duplexes via the minor groove binding resulting in the preference of xT-G over canonical xT-A pair. Interestingly, in this study, the thermal denaturation study revealed different effect of terpene chain length on base-pair specificity in RNA context. Among methyl (C1), dimethylallyl (C5), geranyl (C10) and farnesyl-2-thiouridine (C15), only dimethylallyl (C5) and geranyl (C10) could promote the xU-G base-pair over canonical xU-A base-pair. The molecular dynamics simulations show that the xU-G forms 2-H bonding while xU-A theoretically can form 0.5 H-bonding because of the stacking interaction on the uracil holding the uridine in the helical loop and push the modified terpene group out to the minor groove. The discrimination between xU-G and xU-A are solely from the interaction of hydrophobic chain to the hydrophobic area in the minor groove which resulting from the orientation of the modified uridine base in the RNA duplexes.

Necessity of terpene chain length on base pairing discrimination of nature’s selection S-geranyl-2-thiouridine

256th National Meeting (2018)

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