Control of gene expression by a natural metabolite-responsive ribozyme

Abstract

Most biological catalysts are made of protein; however, eight classes of natural ribozymes have been discovered that catalyse fundamental biochemical reactions. The central functions of ribozymes in modern organisms support the hypothesis that life passed through an ‘RNA world’ before the emergence of proteins and DNA. We have identified a new class of ribozymes that cleaves the messenger RNA of the glmS gene in Gram-positive bacteria. The ribozyme is activated by glucosamine-6-phosphate (GlcN6P), which is the metabolic product of the GlmS enzyme. Additional data indicate that the ribozyme serves as a metabolite-responsive genetic switch that represses the glmS gene in response to rising GlcN6P concentrations. These findings demonstrate that ribozyme switches may have functioned as metabolite sensors in primitive organisms, and further suggest that modern cells retain some of these ancient genetic control systems.

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Figure 1: The glmS motif.
Figure 2: The glmS motif from B. subtilis serves as a metabolite-responsive ribozyme.
Figure 3: Optimization, divalent metal requirements and rapid metabolite induction of the glmS ribozyme.
Figure 4: Ribozyme boundaries and cleavage site chemistry.
Figure 5: Ribozyme function in vitro negatively correlates with gene expression in vivo.

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Acknowledgements

We thank K. Corbino for generating the glmS IGR sequence alignments, and members of the Breaker laboratory for discussions. This work was supported by grants from the NIH and the NSF. R.R.B is also grateful for support from the Yale Liver Center and the David and Lucile Packard Foundation.

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Correspondence to Ronald R. Breaker.

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The authors declare that they have no competing financial interests.

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Winkler, W., Nahvi, A., Roth, A. et al. Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428, 281–286 (2004). https://doi.org/10.1038/nature02362

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