Poster abstracts
Poster number 113 submitted by Md Sharear Saon
Identifying and characterizing shifted G•U wobbles arising from alternative protonation of RNA
Md. Sharear Saon (Deptartment of Chemistry, Pennsylvania State University), Catherine A. Douds (Department of Biochemistry and Molecular Biology, Pennsylvania State University), Andrew J. Veenis (Deptartment of Chemistry, Pennsylvania State University), Ashley N. Pearson (Department of Biology, Pennsylvania State University), Neela Yennawar (Huck Institutes of the Life Sciences, Pennsylvania State University), Philip C. Bevilacqua (Deptartment of Chemistry, Pennsylvania State University)
Abstract:
RNA exhibits diverse functionalities, including those of an enzyme (ribozyme), a molecular sensor (riboswitch), and even a therapeutic agent. It also likely played a central role in the origin of life under the RNA world hypothesis. This functional versatility is remarkable given the relatively limited intrinsic molecular diversity of RNA. While covalent nucleotide modifications have been extensively studied, far less is known about non-covalent alterations of the nucleobases. These non-covalent changes can be classified as novel charged or tautomeric forms of the bases, which involve changes in protonation state and proton location, respectively. Like covalent modifications of RNA, non-covalent modifications may provide additional stability and functionality to the RNA. Here, we applied a cheminformatic approach to identify non-covalent alterations in RNA that support two rare orientations of the G•U wobble base pair. In the first, either the G or U can adopt a deprotonated or rare enol tautomeric form, resulting in a canonical G-C-like geometry, which we annotate as a partially shifted G•U wobble. In the second orientation, only the U adopts a deprotonated or enol tautomeric state, forming a fully shifted G•U wobble in which the O6 atom of G protrudes into the major groove. We provide widespread structural support of these proton-altered G•U wobbles within RNA 3D structures in the Protein Data Bank (1). We suggest that in the first orientation, the G•U wobble could be a source of mutagenesis during replication of RNA viruses. The cheminformatics pipeline developed here can be extended to other non-Watson-Crick-Franklin base pairs to uncover additional hidden protonation states and expand our understanding of RNA structural chemistry.
References:
1. Berman, H.M., Westbrook, J., Feng, Z., Gilliland, G., Bhat, T.N., Weissig, H., Shindyalov, I.N. and Bourne, P.E. (2000) The Protein Data Bank. Nucleic Acids Res., 28, 235-242.
Keywords: Anionic RNA, RNA modifications, cheminformatics