Letters to Nature

Nature 419, 952-956 (31 October 2002) | doi:10.1038/nature01145; Received 2 August 2002; Accepted 20 September 2002; Published online 16 October 2002

Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression

Wade Winkler1, Ali Nahvi2 & Ronald R. Breaker1

  1. Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520-8103, USA
  2. Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208103, New Haven, Connecticut 06520-8103, USA

Correspondence to: Ronald R. Breaker1 Correspondence and requests for materials should be addressed to R.R.B. (e-mail: Email: ronald.breaker@yale.edu).

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.