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

Niu, Xiaolin; Xu, Zhonghe; Zhang, Yufan; Zuo, Xiaobing; Chen, Chunlai; Fang, Xianyang

doi:10.1038/s41467-023-43232-z

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

Journal Article · Wed Nov 15 00:00:00 EST 2023 · Nature Communications

DOI:https://doi.org/10.1038/s41467-023-43232-z· OSTI ID:2470236

^[1]; ^[1]; Zhang, Yufan ^[2]; ^[3]; ^[1]; ^[4]

Tsinghua Univ., Beijing (China)
Chinese Academy of Sciences (CAS), Beijing (China)
Argonne National Laboratory (ANL), Argonne, IL (United States)
Tsinghua Univ., Beijing (China); Chinese Academy of Sciences (CAS), Beijing (China)

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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States); Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: China Postdoctoral Science Foundation; National Key Research and Development Program of China; National Natural Science Foundation of China (NSFC); USDOE; USDOE Office of Science (SC), Basic Energy Sciences (BES)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2470236

Alternate ID(s):: OSTI ID: 2564890

Journal Information:: Nature Communications, Journal Name: Nature Communications Vol. 14; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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

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