Hidden riboswitches

A computational approach has revealed small genetic devices in the DNA of bacteria that had previously gone unnoticed.

Image credit: Arne Hückelheim (CC BY-SA 3.0)

Many bacteria use small genetic devices called riboswitches to sense molecules that are essential for life and regulate the genes necessary to make, break or move these molecules. Riboswitches are made of molecules of RNA and appear to have ancient origins that predate the evolution of bacteria and other lifeforms made of cells. Inside modern bacteria, chunks of DNA in the genome provide the instructions to make riboswitches and around 40 different types of riboswitch have been identified so far. However, it has been proposed that the instructions for thousands more riboswitches may remain hidden in the DNA of bacteria.

All of the currently known riboswitches contain a region called an aptamer that binds to a target molecule. This binding causes another structure in the riboswitch RNA to switch a specific gene on or off. For example, the aptamer binding might cause a hairpin-like structure called a terminator to form, which stops a gene being used to make new RNA molecules.

In 2019 a team of researchers reported using a computational approach to identify new riboswitches in bacteria. This approach identified many different chunks of DNA that might code for a riboswitch, including one known as the thiS motif. This potential new riboswitch appeared to be associated with a gene that encodes a protein required to make a vitamin called thiamin (also known as vitamin B1).

To test the new computational approach, Atilho et al. including several of the researchers involved in the earlier work used genetic and biochemical techniques to study the thiS motif. The experiments revealed that the motif binds to a molecule called HMP-PP, which bacteria use to make thiamin. Unexpectedly, the aptamer of the riboswitch was nested within a terminator, rather than being a separate entity.

The findings of Atilho et al. reveal that riboswitches can be even more compact than previously thought. Furthermore, these findings reveal new insights into how bacteria use riboswitches to manage their vitamin levels. In the future it may be possible to develop drugs that target such riboswitches to starve bacteria of these essential molecules.