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RNA structure probing uncovers RNA structure-dependent biological functions

Nature Chemical Biology volume 17, pages 755–766 (2021)Cite this article

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Abstract

RNA molecules fold into complex structures that enable their diverse functions in cells. Recent revolutionary innovations in transcriptome-wide RNA structural probing of living cells have ushered in a new era in understanding RNA functions. Here, we summarize the latest technological advances for probing RNA secondary structures and discuss striking discoveries that have linked RNA regulation and biological processes through interrogation of RNA structures. In particular, we highlight how different long noncoding RNAs form into distinct secondary structures that determine their modes of interactions with protein partners to realize their unique functions. These dynamic structures mediate RNA regulatory functions through altering interactions with proteins and other RNAs. We also outline current methodological hurdles and speculate about future directions for development of the next generation of RNA structure-probing technologies of higher sensitivity and resolution, which could then be applied in increasingly physiologically relevant studies.

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Fig. 1: Summary of RNA secondary structure-probing methods.
Fig. 2: Recent technological innovations in RNA secondary structure probing.
Fig. 3: Recent technological innovations of crosslinking and proximity ligation-based methods.
Fig. 4: Understanding RNA secondary structures facilitates RNA functional studies.
Fig. 5: RNA regulation revealed by differential RNA structure analysis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (NSFC) (91940303, 31725009, 31830108, 31821004) and the HHMI International Program (55008728) to L.-L.C., and the National Natural Science Foundation of China (Grants No. 91740204, 91940306 and 31761163007) and the State Key Research Development Program of China (Grant No. 2018YFA0107603) to Q.C.Z. L.-L.C. acknowledges the support from the XPLORER PRIZE.

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  1. These authors contributed equally: Xi-Wen Wang, Chu-Xiao Liu.

Authors and Affiliations

  1. MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology and Frontier Research Center for Biological Structure, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China

    Xi-Wen Wang & Qiangfeng Cliff Zhang

  2. Tsinghua-Peking Center for Life Sciences, Beijing, China

    Xi-Wen Wang & Qiangfeng Cliff Zhang

  3. State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China

    Chu-Xiao Liu & Ling-Ling Chen

  4. School of Life Science and Technology, ShanghaiTech University, Shanghai, China

    Ling-Ling Chen

  5. School of Life Sciences, Hangzhou Institute for Advanced Study, University of the Chinese Academy of Sciences, Hangzhou, China

    Ling-Ling Chen

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Wang, XW., Liu, CX., Chen, LL. et al. RNA structure probing uncovers RNA structure-dependent biological functions. Nat Chem Biol 17, 755–766 (2021). https://doi.org/10.1038/s41589-021-00805-7

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