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Scripps Research study sheds light on RNA 'on/off switches'

pes of RNA molecules are adept at performing feats worthy of their protein counterparts. Riboswitches are one such example.

Discovered only about eight years ago, riboswitches are short stretches of RNA that reside within the messenger RNAs of proteins involved in a cell's metabolism. These riboswitches bind certain metabolites and, depending on how much binding occurs, the riboswitches turn the production of the corresponding proteins on or off.

Until now, most researchers had assumed a single riboswitch was specific for a single metabolite. But the new study by Fedor's group shows a riboswitch can incorporate signals from many metabolites at once.

A Self-Destructing Riboswitch

Fedor's group was interested in studying the function of a type of riboswitch that binds to a metabolite called glucosamine-6-phosphate. This amino sugar, a building block for many glyosides and glycans, is required for the cell wall and other vital structures in bacterial cells.

This particular riboswitch resides in the messenger RNA that carries instructions for the enzyme responsible for the production of glucosamine-6-phosphate, called GlmS. It was known that when glucosamine-6-phosphate is abundant in a cell, the riboswitch stops production of the GlmS enzyme by destroying itself and its messenger RNA. This self-destruction functions to shut off any more production of glucosamine-6-phosphate.

On the other hand, when glucosamine-6-phosphate concentrations are low, the glmS riboswitch does not self-destruct, keeping the messenger RNA functioning.

A Puzzling Observation

Fedor and graduate student Peter Watson had designed an assay to measure the amounts of the glmS riboswitch in yeast cells as they added increasing concentrations of glucosamine. But the scientists stumbled on a puzzling finding.

If they grew their yeast in energy-rich broth that contained glycerol, a 3-carbon energy source, th

Contact: Mika Ono
Scripps Research Institute

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