IIIT Hyderabad Publications
Role of Reverse Watson-Crick Purine-Purine Base Pairs in Functional RNAs
Author: abhinav Mittal
Report no: IIIT/TH/2016/59
Identification of static and/or dynamic roles of different non-canonical base pairs is essential for a comprehensive understanding of the sequence-structure-function space of RNA. In the past combined structural bioinformatic and quantum mechanical (QM) approach provided insights into occurrence context and conservation and covariation pattern of non-canonical A:G W:W Cis base pair in RNAs. In this work we have investigated structural and functional occurrence context of reverse Watson-Crick purine-purine base pairs (A:A, G:G and A:G W:W Trans) which constitute an interesting class of non-canonical base pairs in RNA due to their characteristic C10-C10 distance (highest among all base pairing geometries) and parallel local strand orientation. In contrast to canonical base pairs, intrinsic interaction energies and frequencies of occurrence in a nonredundant set of RNA crystal structures of these base pairs do not correlate with each other. Therefore, it is expected that, occurrence of these base pairs will be associated with specific structural folds or functional roles. We have identified the occurrences of these base pairs in a non-redundant set of RNA crystal structures and performed structural alignments of the corresponding homologous sites followed by a detailed context analysis. Our studies reveal that occurrences of purine-purine W:W Trans pairs exhibit a bimodal distribution with respect to the corresponding local backbone geometry. One mode is populated by both A:A and G:G W:W Trans pairs and characterized by a special fold in backbone. We call it a ‘Sharp-turn’ motif. We have observed ‘Sharp-turn’ to be of significant biological importance as it acts as binding site for proteins, metabolites and ions in RNAs. It remains conserved across species with some variation in its composition and often mediates structural folds crucial for the function as in the case of HIV-1 dimerization initiation site. The other mode in distribution is explicitly associated to A:A W:W Trans pairs involved in mediating higher order interactions. A:A W:W Trans mediates in these higher order interactions by participating in specific kinds of triple/quartet formation. We also have analyzed structural context of previously undetected A:G W:W Trans base pair. It has been found to be involved in maintaining translational fidelity at A site in the ribosome via type II A-minor and G-minor interactions with codon:anticodon bases. We rationalize our observations on the basis of quantum chemical calculations performed at M05-2X/6-3++(2d,2p) level of theory. The general trends obtained from analyzing X-ray crystal structures are also consistent with trends observed in available solution NMR structures.
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Centre for Computational Natural Sciences and Bioinformatics
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