(467h) Conformational and Energetic Effects Associated with Methylation in RNA

Post-transcriptional modifications in RNA play an essential role in various cellular processes, including gene regulation, transcription, and translation as well as in the development of various diseases. Currently, hundreds of chemical modifications have been identified in RNA molecules ranging from methylation to more complex chemical modifications. Despite recent advancements in the mass-spectrometry and sequencing technologies which enabled identification and characterization of post-transcriptional modifications in RNA, a full understanding of the effects of modifications on the RNA structure, folding, and dynamics remains elusive. In this work, atomistic simulations were utilized to enhance our understanding of the structural and conformational effects of methylation, the most abundant modification in RNA molecules. Initially, the energetics and dynamics of syn/anti rotational isomers of the methyl group in the methylated adenine mononucleotide were characterized, thus resolving the effects of methylation on one of the basic building blocks of RNA. Then, an RNA hairpin capped by a methylated tetraloop motif was studied, a commonly observed structural motif in RNA consisting of four nucleotides which serves as a recognition site for proteins. Methylation of the tetraloop was identified to enhance its flexibility, thereby revealing conformations accessible to the reader protein. These results highlight the importance of conformational and energetic effects in RNA which are induced by chemical modifications to its nucleotides.