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).

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 ribozyme^{1, 2} and receptor^{3, 4} elements that exhibit considerable enzymatic power and binding specificity. Moreover, these activities can be combined to create allosteric ribozymes^{5, 6} that are modulated by effector molecules. It has also been proposed^{7, 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.

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).