Direct observation of tRNA-chaperoned folding of a dynamic mRNA ensemble

Suddala, Krishna C.; Yoo, Janghyun; Fan, Lixin; Zuo, Xiaobing; Wang, Yun-Xing; Chung, Hoi Sung; Zhang, Jinwei

doi:10.1038/s41467-023-41155-3

Direct observation of tRNA-chaperoned folding of a dynamic mRNA ensemble

Journal Article · Wed Sep 06 00:00:00 EDT 2023 · Nature Communications

DOI:https://doi.org/10.1038/s41467-023-41155-3· OSTI ID:2404987

^[1]; ^[1]; Fan, Lixin ^[2]; ^[3]; ^[2]; ^[1]; ^[1]

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States)
National Cancer Institute, Frederick, MD (United States). Small-Angle X-Ray Scattering (SAXS) Core Facility
Argonne National Laboratory (ANL), Argonne, IL (United States)

T-box riboswitches are multi-domain noncoding RNAs that surveil individual amino acid availabilities in most Gram-positive bacteria. T-boxes directly bind specific tRNAs, query their aminoacylation status to detect starvation, and feedback control the transcription or translation of downstream amino-acid metabolic genes. Most T-boxes rapidly recruit their cognate tRNA ligands through an intricate three-way stem I-stem II-tRNA interaction, whose establishment is not understood. Using single-molecule FRET, SAXS, and time-resolved fluorescence, we find that the free T-box RNA assumes a broad distribution of open, semi-open, and closed conformations that only slowly interconvert. tRNA directly binds all three conformers with distinct kinetics, triggers nearly instantaneous collapses of the open conformations, and returns the T-box RNA to their pre-binding conformations upon dissociation. This scissors-like dynamic behavior is enabled by a hinge-like pseudoknot domain which poises the T-box for rapid tRNA-induced domain closure. This study reveals tRNA-chaperoned folding of flexible, multi-domain mRNAs through a Venus flytrap-like mechanism.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2404987

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 14; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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non-coding RNAs
riboswitches
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Direct observation of tRNA-chaperoned folding of a dynamic mRNA ensemble

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