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Structure-based insights into recognition and regulation of SAM-sensing riboswitches

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Abstract

Riboswitches are highly conserved RNA elements that located in the 5′-UTR of mRNAs, which undergo real-time structure conformational change to achieve the regulation of downstream gene expression by sensing their cognate ligands. S-adenosylmethionine (SAM) is a ubiquitous methyl donor for transmethylation reactions in all living organisms. SAM riboswitch is one of the most abundant riboswitches that bind to SAM with high affinity and selectivity, serving as regulatory modules in multiple metabolic pathways. To date, seven SAM-specific riboswitch classes that belong to four families, one SAM/SAH riboswitch and one SAH riboswitch have been identified. Each SAM riboswitch family has a well-organized tertiary core scaffold to support their unique ligand-specific binding pocket. In this review, we summarize the current research progress on the distribution, structure, ligand recognition and gene regulation mechanism of these SAM-related riboswitch families, and further discuss their evolutionary prospects and potential applications.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (32022039, 31870810, 91940302, 91640104), the National Key Research and Development Project of China (2021YFC2300300), the China Postdoctoral Science Foundation (2022M713637), the Outstanding Youth Fund of Zhejiang Province (LR19C050003), and the Fundamental Research Funds for the Central Universities (2017QN81010).

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  1. Department of Gastroenterology, Department of Cardiology of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310058, China

    Luqian Zheng & Aiming Ren

  2. Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China

    Luqian Zheng, Qianqian Song, Xiaochen Xu, Xin Shen, Chunyan Li, Hongcheng Li, Hao Chen & Aiming Ren

  3. The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518033, China

    Luqian Zheng

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Zheng, L., Song, Q., Xu, X. et al. Structure-based insights into recognition and regulation of SAM-sensing riboswitches. Sci. China Life Sci. 66, 31–50 (2023). https://doi.org/10.1007/s11427-022-2188-7

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