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

• Published in: iScience 2020-12, Vol.23 (12), p.101866-101866, Article 101866
• Main Authors: Haruehanroengra, Phensinee, Vangaveti, Sweta, Ranganathan, Srivathsan V., Mao, Song, Su, Max Daniel, Chen, Alan A., Sheng, Jia
• Format: Article
• Language: English
• Subjects: Biochemistry; Molecular Structure; Structural Biology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2020.101866

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. [Display omitted] •Geranyl group on ges2U has perfect length to enhance binding to G over A in RNA•Other ges2U analogues has no pairing preference between G or A•MD shows the molecular dynamic behavior of different terpene chains in RNA duplex Biochemistry; Molecular Structure; Structural Biology