Allosteric Modulation of the Faecalibacterium prausnitzii Hepatitis Delta Virus-like Ribozyme by Glucosamine 6-Phosphate: The Substrate of the Adjacent Gene Product.
- Author(s): Passalacqua, Luiz FM
- Jimenez, Randi M
- Fong, Jennifer Y
- Lupták, Andrej
- et al.
Published Web Locationhttps://doi.org/10.1021/acs.biochem.7b00879
Self-cleaving ribozymes were discovered 30 years ago and have been found throughout nature, from bacteria to animals, but little is known about their biological functions and regulation, particularly how cofactors and metabolites alter their activity. A hepatitis delta virus-like self-cleaving ribozyme maps upstream of a phosphoglucosamine mutase (glmM) open reading frame in the genome of the human gut bacterium Faecalibacterium prausnitzii. The presence of a ribozyme in the untranslated region of glmM suggests a regulation mechanism of gene expression. In the bacterial hexosamine biosynthesis pathway, the enzyme glmM catalyzes the isomerization of glucosamine 6-phosphate into glucosamine 1-phosphate. In this study, we investigated the effect of these metabolites on the co-transcriptional self-cleavage rate of the ribozyme. Our results suggest that glucosamine 6-phosphate, but not glucosamine 1-phosphate, is an allosteric ligand that increases the self-cleavage rate of drz-Fpra-1, providing the first known example of allosteric modulation of a self-cleaving ribozyme by the substrate of the adjacent gene product. Given that the ribozyme is activated by the glmM substrate, but not the product, this allosteric modulation may represent a potential feed-forward mechanism of gene expression regulation in bacteria.