Do mRNAs act as direct sensors of small molecules to control their expression?

The paper in this issue of PNAS by Miranda-Rios et al. (1) demonstrates the importance of a conserved RNA structure in the regulation of genes involved in thiamin biosynthesis. Thiamin, also known as vitamin B1, is a cofactor for many important enzymes and therefore essential for growth. Bacteria have genes for all the enzymes necessary to synthesize thiamin, but if adequate amounts are present in the environment, they can use those rather than make their own, saving the energy and materials that would otherwise be used for synthesis. Such feedback inhibition, where the product of a pathway can repress the expression of the enzymes in the pathway, is quite common in bacteria. Many of the most interesting results in molecular biology over the past 50 years have come from unraveling the mechanisms of such feedback regulation. Although bacteria, at least many species, have the ability to make all of the complex molecules they need for growth from simple compounds, they can also use environmental sources of those molecules and, in doing so, repress synthesis of the genes required to make them. Such a regulatory response requires, at a minimum, a means of sensing the concentration of the product and a mechanism to control the expression of the relevant genes that depends on that concentration. In the case of thiamin regulation, the data suggest that the mRNA for the synthesizing enzymes may itself serve as the sensor and provide the mechanism for regulation. Although each regulatory feedback loop has its own features, some mechanisms are quite common. Typically, there is a regulatory protein that can sense the level of the product and then bind to the DNA or RNA to affect the expression of the relevant enzymes. For example, the trp repressor of Escherichia coli binds to DNA only …