Energy-sensing switch that can be target for antibiotics found

Biochemists from The Scripps Research Institute (TSRI) have discovered a genetic sequence that can alter its host gene's activity in response to cellular energy levels.

Discovery of similar energy-sensing switches can be useful for treating metabolism-related disorders such as type 2 diabetes and heart disease.

"This discovery adds a new dimension to our understanding of how cells sense and manage their energy levels, which is one of the most important processes in biology," said the study's senior author, Martha J Fedor.

This type of gene-switching sequence is known as a riboswitch because it appears on the strand of ribonucleic acid (RNA) that is first transcribed from a gene's DNA.

Unlike other known riboswitches, which have relatively limited functions, this one acts as a sensor for the basic molecular fuel that powers all living cells and controls many genes.

The newly discovered riboswitch detects a small molecule known as adenosine triphosphate (ATP), the standard unit of chemical energy in all known organisms on our planet.

Scientists had thought that cells use only large and relatively complex proteins to sense these all-important energy molecules and adjust cell activities accordingly.

"This is the first riboswitch that is known to be involved in global metabolic regulation," said Fedor.

"It opens up the possibility that RNA switches are involved in the general regulation of metabolism," Fedor said in a statement.

The team discovered a stretch of apparent ATP-binding RNA known as the ydaO motif. Researcher Peter Y Watson performed structure-mapping analyses of ydaO to confirm that it binds to ATP and to determine precisely where it binds.

Attaching ydaO to a "reporter" gene, he found that in bacterial cells, the reporter gene's expression level stayed low when ATP levels were normal and rose sharply when ATP levels dropped