Dataset Information

Terpene Chain Length Affects the Base Pairing Discrimination of S-geranyl-2-thiouridine in RNA Duplex.

ABSTRACT: Geranylation is a hydrophobic modification discovered in several bacteria tRNAs with the function of promoting codon bias during translation. However, why nature selects this C10-geranyl group remains a question. We conduct synthesis, UV-thermal denaturation, and molecular simulation studies in RNA duplexes and reveal possible reasons behind this natural selection. Among methyl-(C1), dimethylallyl-(C5), geranyl-(C10), and farnesyl-(C15) modified 2-thiouridines, only geranyl-group promotes U:G over U:A pair. Molecular simulation shows all the modified terpene groups point to the minor groove of RNA duplexes. The discrimination between U:G and U:A pairs derives from the difference in hydrogen bonding and interactions of the chain with the hydrophobic area in the minor groove. Geranyl group has perfect length to discriminate U:G and U:A pairs, whereas the others are either too long or too short to achieve the same behavior. This work indicates that geranyl group cannot be replaced by other terpene groups in promoting codon-specificity.

SUBMITTER: Haruehanroengra P

PROVIDER: S-EPMC7726334 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Terpene Chain Length Affects the Base Pairing Discrimination of <i>S</i>-geranyl-2-thiouridine in RNA Duplex.

Haruehanroengra Phensinee P Vangaveti Sweta S Ranganathan Srivathsan V SV Mao Song S Su Max Daniel MD Chen Alan A AA Sheng Jia J

iScience 20201126 12

Geranylation is a hydrophobic modification discovered in several bacteria tRNAs with the function of promoting codon bias during translation. However, why nature selects this C10-geranyl group remains a question. We conduct synthesis, UV-thermal denaturation, and molecular simulation studies in RNA duplexes and reveal possible reasons behind this natural selection. Among methyl-(C1), dimethylallyl-(C5), geranyl-(C10), and farnesyl-(C15) modified 2-thiouridines, only geranyl-group promotes U:G ov ...[more]

PMID: 33319183

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Project description:The exocyclic 1, N(2)-ethenodeoxyguanosine (1,N(2)-is an element of dG) adduct, arising from the reaction of vinyl halides and other vinyl monomers, including chloroacetaldehyde, and lipid peroxidation products with dG, was examined at pH 5.2 in the oligodeoxynucleotide duplex 5'-d(CGCATXGAATCC)-3'.5'-d(GGATTCCATGCG)-3' (X = 1,N(2)-is an element of dG). Previously, X(anti).C(anti) pairing was established in this duplex, containing the 5'-TXG-3' sequence context, at pH 8.6 [Shanmugam, G., Goodenough, A. K., Kozekov, I. D., Harris, T. M., Guengerich, F. P., Rizzo, C. J., and Stone, M. P. (2007) Chem. Res. Toxicol. 20, 1601- 1611]. At pH 5.2, the 1,N(2)-is an element of dG adduct decreased the thermal stability of the duplex by approximately 13 degrees C. The 1,N(2)-is an element of dG adduct rotated about the glycosyl bond from the anti to the syn conformation. This resulted in the observation of a strong nuclear Overhauser effect (NOE) between the imidazole proton of 1,N(2)-is an element of dG and the anomeric proton of the attached deoxyribose, accompanied by an NOE to the minor groove A(20) H2 proton from the complementary strand. The syn conformation of the glycosyl bond at 1,N(2)-is an element of dG placed the exocyclic etheno moiety into the major groove. This resulted in the observation of NOEs between the etheno protons and the major groove protons of the 5'-neighboring thymine. The 1,N(2)-is an element of dG adduct formed a Hoogsteen pair with the complementary cytosine, characterized by downfield shifts of the amino protons of the cytosine complementary to the exocyclic adduct. The pattern of chemical shift perturbations indicated that the lesion introduced a localized structural perturbation involving the modified base pair and its 3'- and 5'-neighbor base pairs. A second conformational equilibrium was observed, in which both the modified base pair and its 3'-neighboring G.C base pair formed tandem Hoogsteen pairs. The results support the conclusion that at neutral pH, in the 5'-TXG-3' sequence, the 1,N(2)-is an element of dG adduct exists as a blend of conformations in duplex DNA. These involve the interconversion of the glycosyl torsion angle between the anti and the syn conformations, occurring at an intermediate rate on the NMR time scale.

Dataset Information

Terpene Chain Length Affects the Base Pairing Discrimination of S-geranyl-2-thiouridine in RNA Duplex.

Publications

Terpene Chain Length Affects the Base Pairing Discrimination of <i>S</i>-geranyl-2-thiouridine in RNA Duplex.

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