Structural and dynamic mechanisms for coupled folding and tRNA recognition of a translational T-box riboswitch

Xiaolin Niu, Zhonghe Xu, Yufan Zhang, Xiaobing Zuo, Chunlai Chen () and Xianyang Fang ()
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Xiaolin Niu: Tsinghua University
Zhonghe Xu: Tsinghua University
Yufan Zhang: Institute of Biophysics, Chinese Academy of Sciences
Xiaobing Zuo: Argonne National Laboratory
Chunlai Chen: Tsinghua University
Xianyang Fang: Tsinghua University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract T-box riboswitches are unique riboregulators where gene regulation is mediated through interactions between two highly structured RNAs. Despite extensive structural insights, how RNA-RNA interactions drive the folding and structural transitions of T-box to achieve functional conformations remains unclear. Here, by combining SAXS, single-molecule FRET and computational modeling, we elaborate the folding energy landscape of a translational T-box aptamer consisting of stems I, II and IIA/B, which Mg2+-induced global folding and tRNA binding are cooperatively coupled. smFRET measurements reveal that high Mg2+ stabilizes IIA/B and its stacking on II, which drives the pre-docking of I and II into a competent conformation, subsequent tRNA binding promotes docking of I and II to form a high-affinity tRNA binding groove, of which the essentiality of IIA/B and S-turn in II is substantiated with mutational analysis. We highlight a delicate balance among Mg2+, the intra- and intermolecular RNA-RNA interactions in modulating RNA folding and function.

Date: 2023
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DOI: 10.1038/s41467-023-43232-z

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