Structure and mechanism of a methyltransferase ribozyme

作者：Jie Deng, Timothy J. Wilson, Jia Wang, Xuemei Peng, Mengxiao Li, Xiaowei Lin, Wenjian Liao, David M.J. Lilley, Lin Huang · 发表于：Nature Chemical Biology · 年份：2022 · DOI：10.1038/s41589-022-00982-z · 被引用次数：44 · 研究领域：RNA modifications and cancer、RNA and protein synthesis mechanisms、DNA and Nucleic Acid Chemistry

Known ribozymes in contemporary biology perform a limited range of chemical catalysis, but in vitro selection has generated species that catalyze a broader range of chemistry; yet, there have been few structural and mechanistic studies of selected ribozymes. A ribozyme has recently been selected that can catalyze a site-specific methyl transfer reaction. We have solved the crystal structure of this ribozyme at a resolution of 2.3 Å, showing how the RNA folds to generate a very specific binding site for the methyl donor substrate. The structure immediately suggests a catalytic mechanism involving a combination of proximity and orientation and nucleobase-mediated general acid catalysis. The mechanism is supported by the pH dependence of the rate of catalysis. A selected methyltransferase ribozyme can thus use a relatively sophisticated catalytic mechanism, broadening the range of known RNA-catalyzed chemistry.