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Advances and opportunities in RNA structure experimental determination and computational modeling

Nature Methods volume 19, pages 1193–1207 (2022)Cite this article

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Abstract

Beyond transferring genetic information, RNAs are molecules with diverse functions that include catalyzing biochemical reactions and regulating gene expression. Most of these activities depend on RNAs’ specific structures. Therefore, accurately determining RNA structure is integral to advancing our understanding of RNA functions. Here, we summarize the state-of-the-art experimental and computational technologies developed to evaluate RNA secondary and tertiary structures. We also highlight how the rapid increase of experimental data facilitates the integrative modeling approaches for better resolving RNA structures. Finally, we provide our thoughts on the latest advances and challenges in RNA structure determination methods, as well as on future directions for both experimental approaches and artificial intelligence-based computational tools to model RNA structure. Ultimately, we hope the technological advances will deepen our understanding of RNA biology and facilitate RNA structure-based biomedical research such as designing specific RNA structures for therapeutics and deploying RNA-targeting small-molecule drugs.

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Fig. 1: Advances in experimental RNA structure determination.
Fig. 2: The computational methods for RNA secondary structure modeling.
Fig. 3: The computational methods for RNA tertiary structure modeling.
Fig. 4: Integrative computational methods for RNA secondary structure modeling based on experimental probing data.
Fig. 5: Integrative computational methods for RNA tertiary structure modeling based on experimental probing data.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (grants nos. 32125007 and 91940306 to Q.C.Z., and 32100504 to Y.F.), the Postdoctoral Science Foundation of China (2021M691811 to Y.F., and 2021M690091 and 2021T140380 to L.S.) and the Postdoctoral Foundation of Tsinghua-Peking Center for Life Sciences (J.Z., Y.F. and L.S.).

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  1. These authors contributed equally: Jinsong Zhang, Yuhan Fei.

Authors and Affiliations

  1. MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, School of Life Sciences, Tsinghua University, Beijing, China

    Jinsong Zhang, Yuhan Fei, Lei Sun & Qiangfeng Cliff Zhang

  2. Beijing Advanced Innovation Center for Structural Biology & Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China

    Jinsong Zhang, Yuhan Fei, Lei Sun & Qiangfeng Cliff Zhang

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

    Jinsong Zhang, Yuhan Fei, Lei Sun & Qiangfeng Cliff Zhang

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  1. Jinsong Zhang
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  2. Yuhan Fei
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  3. Lei Sun
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  4. Qiangfeng Cliff Zhang
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Correspondence to Lei Sun or Qiangfeng Cliff Zhang.

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Zhang, J., Fei, Y., Sun, L. et al. Advances and opportunities in RNA structure experimental determination and computational modeling. Nat Methods 19, 1193–1207 (2022). https://doi.org/10.1038/s41592-022-01623-y

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