National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM118070
United States
Howard Hughes Medical Institute (HHMI)
Hanna H. Gray Postdoctoral Fellowship
United States
Citation
Journal: Sci Adv / Year: 2022 Title: Cryo-EM reveals an entangled kinetic trap in the folding of a catalytic RNA. Authors: Steve L Bonilla / Quentin Vicens / Jeffrey S Kieft / Abstract: Functional RNAs fold through complex pathways that can contain misfolded "kinetic traps." A complete model of RNA folding requires understanding the formation of these misfolded states, but they are ...Functional RNAs fold through complex pathways that can contain misfolded "kinetic traps." A complete model of RNA folding requires understanding the formation of these misfolded states, but they are difficult to characterize because of their transient and potentially conformationally dynamic nature. We used cryo-electron microscopy (cryo-EM) to visualize a long-lived misfolded state in the folding pathway of the group I intron, a paradigmatic RNA structure-function model system. The structure revealed how this state forms native-like secondary structure and tertiary contacts but contains two incorrectly crossed strands, consistent with a previous model. This incorrect topology mispositions a critical catalytic domain and cannot be resolved locally as extensive refolding is required. This work provides a structural framework for interpreting decades of biochemical and functional studies and demonstrates the power of cryo-EM for the exploration of RNA folding pathways.
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