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The case of the missing allosteric ribozymes

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Abstract

The RNA World theory encompasses the hypothesis that sophisticated ribozymes and riboswitches were the primary drivers of metabolic processes in ancient organisms. Several types of catalytic RNAs and many classes of ligand-sensing RNA switches still exist in modern cells. Curiously, allosteric ribozymes formed by the merger of RNA enzyme and RNA switch components are largely absent in today’s biological systems. This is true despite the striking abundances of various classes of both self-cleaving ribozymes and riboswitch aptamers. Here we present the known types of ligand-controlled ribozymes and riboswitches and discuss the possible reasons why fused ribozyme–aptamer constructs have been disfavored through evolution.

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Fig. 1: The known classes of natural ribozymes and riboswitches.
Fig. 2: General architectures of engineered and natural ligand-controlled ribozymes.
Fig. 3: Two predominant expression platform mechanisms for riboswitches.
Fig. 4: Types of ribozyme naturally regulated by the binding of small molecules.
Fig. 5: A true allosteric ribozyme formed by a single RNA transcript.

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Acknowledgements

We thank K. Harris, A. Roth, N. Sudarsan and Y. Yang for critically reading the manuscript. This work was supported by NIH grants (GM022778 and AI136794) as well as funds from Howard Hughes Medical Institute.

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  1. Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

    Shanker S. S. Panchapakesan & Ronald R. Breaker

  2. Howard Hughes Medical Institute, Yale University, New Haven, CT, USA

    Ronald R. Breaker

  3. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA

    Ronald R. Breaker

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Correspondence to Ronald R. Breaker.

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Panchapakesan, S.S.S., Breaker, R.R. The case of the missing allosteric ribozymes. Nat Chem Biol 17, 375–382 (2021). https://doi.org/10.1038/s41589-020-00713-2

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