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SAM-VI riboswitch structure and signature for ligand discrimination

Author

Listed:
  • Aiai Sun

    (Life Sciences Institute, Zhejiang University)

  • Catherina Gasser

    (Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University)

  • Fudong Li

    (National Science Center for Physical Sciences at Microscale Division of Molecular & Cell Biophysics and School of Life Sciences, University of Science and Technology of China)

  • Hao Chen

    (Life Sciences Institute, Zhejiang University)

  • Stefan Mair

    (Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University)

  • Olga Krasheninina

    (Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University)

  • Ronald Micura

    (Institute of Organic Chemistry, Center for Molecular Biosciences Innsbruck, Leopold Franzens University)

  • Aiming Ren

    (Life Sciences Institute, Zhejiang University)

Abstract

Riboswitches are metabolite-sensing, conserved domains located in non-coding regions of mRNA that are central to regulation of gene expression. Here we report the first three-dimensional structure of the recently discovered S-adenosyl-L-methionine responsive SAM-VI riboswitch. SAM-VI adopts a unique fold and ligand pocket that are distinct from all other known SAM riboswitch classes. The ligand binds to the junctional region with its adenine tightly intercalated and Hoogsteen base-paired. Furthermore, we reveal the ligand discrimination mode of SAM-VI by additional X-ray structures of this riboswitch bound to S-adenosyl-L-homocysteine and a synthetic ligand mimic, in combination with isothermal titration calorimetry and fluorescence spectroscopy to explore binding thermodynamics and kinetics. The structure is further evaluated by analysis of ligand binding to SAM-VI mutants. It thus provides a thorough basis for developing synthetic SAM cofactors for applications in chemical and synthetic RNA biology.

Suggested Citation

  • Aiai Sun & Catherina Gasser & Fudong Li & Hao Chen & Stefan Mair & Olga Krasheninina & Ronald Micura & Aiming Ren, 2019. "SAM-VI riboswitch structure and signature for ligand discrimination," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13600-9
    DOI: 10.1038/s41467-019-13600-9
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    Cited by:

    1. Krishna C. Suddala & Janghyun Yoo & Lixin Fan & Xiaobing Zuo & Yun-Xing Wang & Hoi Sung Chung & Jinwei Zhang, 2023. "Direct observation of tRNA-chaperoned folding of a dynamic mRNA ensemble," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Yanyan Xue & Jun Li & Dian Chen & Xizhu Zhao & Liang Hong & Yu Liu, 2023. "Observation of structural switch in nascent SAM-VI riboswitch during transcription at single-nucleotide and single-molecule resolution," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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