Biochemistry

Rethinking Riboswitch Regulation

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Science  04 Mar 2011:
Vol. 331, Issue 6021, pp. 1115
DOI: 10.1126/science.331.6021.1115-b

The enzyme glucosamine-6-phosphate (GlcN6P) synthase (GlmS) is an important point of metabolic control in the synthesis of amino sugars: essential precursors in the biosynthesis of bacterial cell walls. GlmS gene expression is regulated by the glmS riboswitch, a sequence in the 5′ untranslated region of the mRNA that is also a ribozyme. Binding of GlcN6P activates glmS self-cleavage and this negatively regulates expression of GlmS.

Watson and Fedor now reveal another level of complexity to riboswitch regulation. By growing yeast on various carbon sources and then measuring the ligand concentration dependence of intracellular cleavage kinetics, they found that products of hexose metabolism can competitively inhibit GlcN6P-induced self-cleavage. These results were confirmed in the Gram-positive bacterium Bacillus subtilis, the natural biological context for the riboswitch. These findings suggest that the glmS riboswitch might integrate chemical signals to modulate gene expression in response to the overall metabolic state of the cell.

Nat. Struct. Mol. Biol. 18, 10.1038/nsmb.1989 (2011).

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