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Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression

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Listed:
  • Wade Winkler

    (Yale University)

  • Ali Nahvi

    (Yale University)

  • Ronald R. Breaker

    (Yale University)

Abstract

Although proteins fulfil most of the requirements that biology has for structural and functional components such as enzymes and receptors, RNA can also serve in these capacities. For example, RNA has sufficient structural plasticity to form ribozyme1,2 and receptor3,4 elements that exhibit considerable enzymatic power and binding specificity. Moreover, these activities can be combined to create allosteric ribozymes5,6 that are modulated by effector molecules. It has also been proposed7,8,9,10,11,12 that certain messenger RNAs might use allosteric mechanisms to mediate regulatory responses depending on specific metabolites. We report here that mRNAs encoding enzymes involved in thiamine (vitamin B1) biosynthesis in Escherichia coli can bind thiamine or its pyrophosphate derivative without the need for protein cofactors. The mRNA–effector complex adopts a distinct structure that sequesters the ribosome-binding site and leads to a reduction in gene expression. This metabolite-sensing regulatory system provides an example of a ‘riboswitch’ whose evolutionary origin might pre-date the emergence of proteins.

Suggested Citation

  • Wade Winkler & Ali Nahvi & Ronald R. Breaker, 2002. "Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression," Nature, Nature, vol. 419(6910), pages 952-956, October.
  • Handle: RePEc:nat:nature:v:419:y:2002:i:6910:d:10.1038_nature01145
    DOI: 10.1038/nature01145
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    Cited by:

    1. Arjun Patel & Dominic McGrosso & Ying Hefner & Anaamika Campeau & Anand V. Sastry & Svetlana Maurya & Kevin Rychel & David J. Gonzalez & Bernhard O. Palsson, 2024. "Proteome allocation is linked to transcriptional regulation through a modularized transcriptome," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Singh, Vijai & Chaudhary, Dharmendra Kumar & Mani, Indra & Dhar, Pawan Kumar, 2016. "Recent advances and challenges of the use of cyanobacteria towards the production of biofuels," Renewable and Sustainable Energy Reviews, Elsevier, vol. 60(C), pages 1-10.
    3. Mario A Marchisio & Jörg Stelling, 2011. "Automatic Design of Digital Synthetic Gene Circuits," PLOS Computational Biology, Public Library of Science, vol. 7(2), pages 1-13, February.

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