Topological crossing in the misfolded Tetrahymena ribozyme resolved by cryo-EM

By Shanshan Li, Michael Z. Palo, Grigore D. Pintilie, Xiaojing Zhang, Zhaoming Su, K. Kappel, Wah Chiu, Kaiming Zhang, Rhiju Das. 2022

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Significance Taking advantage of single-particle cryogenic electron microscopy (cryo-EM) to analyze highly heterogeneous or flexible samples, we obtained long-awaited three-dimensional (3D) structures of the misfolded Tetrahymena ribozyme. These structures provide clear evidence for a previously proposed topological isomer model, in which the stereochemically impossible crossing of two core RNA strands prevents rapid rearrangement of the misfolded state to the native state. Topological isomers may be widespread in misfolding of complex RNA, and these cryo-EM structures set a foundation for dissecting their detailed kinetic mechanisms and functional consequences in a paradigmatic model system.

Subfields: Ecology, Molecular Biology

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