Terpene Chain Length Affects the Base Pairing Discrimination of S-geranyl-2-thiouridine in RNA Duplex
Phensinee Haruehanroengra,
Sweta Vangaveti,
Srivathsan V. Ranganathan,
Song Mao,
Max Daniel Su,
Alan A. Chen,
Jia Sheng
Affiliations
Phensinee Haruehanroengra
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA; The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA
Sweta Vangaveti
The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA
Srivathsan V. Ranganathan
The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA
Song Mao
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA; The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA
Max Daniel Su
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA; The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA
Alan A. Chen
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA; The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA
Jia Sheng
Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany, NY 12222, USA; The RNA Institute, University at Albany, State University of New York, Albany, NY 12222, USA; Corresponding author
Summary: 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.
