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

iScience (Dec 2020)

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

Journal volume & issue: Vol. 23, no. 12
p. 101866

Abstract

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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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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