Molecular Level Understanding Of Modified Base Pairs Nucleobase Ligand Pseudo Pairs And Associated Higher Order Structures In Functional RNA

Abstract

Although tremendous progress has been achieved towards understanding the biochemical newlineversatility and biological functions of RNA, there is a need to deepen our understanding of the newlineprinciples governing the structural and functional diversity of these fascinating newlinebiomacromolecules. One possible factor that contributes to the structural diversity of RNA is the newlinepresence of a variety of post-transcriptional modifications of the canonical nucleobases. Detailed newlineanalysis of the role of noncovalent interactions involving modified nucleobases in RNA is thus, newlineexpected to contribute to our understanding of the factors governing the structure and dynamics of newlineRNA. In an attempt to contribute towards this theme, the present work employs a combination of newlinesequence and structural bioinformatics techniques, along with quantum chemical calculations to newlineunderstand the structure and strength of hydrogen bonded pairs and higher order structures newlineinvolving post-transcriptionally modified nucleobases that are present in RNA macromolecular newlinecrystal structures. In addition to highlighting the important structural roles some of these hydrogen newlinebonded entities in RNA molecules, our studies highlight the need for, and providing a newlinecomprehensive approach towards further investigations on such interactions in the context of many newlinebiological processes involving RNA. In addition to understanding the role of posttranscriptional newlinemodifications in RNA, we explored the structural and functional diversity exhibited by newlineriboswitches, non-coding RNA, a class of RNA molecules that are a part of RNA regulatory newlinenetworks, which specifically binds to small cognate ligands and regulate their turnover. Using QM newlineand MD simulations, we explored the molecular features responsible for ligand recognition, and newlinethe associated role of noncovalent interactions in gene regulation by riboswitches. Overall, the newlinethesis contributes towards understanding the structure-functional relationships in RNA newlinemacromolecules. newline