RNA switches can detect iron

RNA elements are important players in the complex game of genetic regulation, sensing the biochemical environment and modulating protein production accordingly. Now researchers have found a new category of riboswitches that sense iron (Nat. Chem. Biol. 2020, DOI: 10.1038/s41589-020-00665-7). Their findings may be used to design new biosensors for metal ions.

A team led by Arati Ramesh, a biochemist at India’s National Centre for Biological Sciences, discovered the new iron-binding riboswitches while investigating their cousin—a cobalt-and-nickel-sensitive riboswitch called NiCo, which is usually found at the tail of a messenger RNA. Another group, at the Pennsylvania State University, has found that one NiCo switch can bind iron (Biochemistry 2020, DOI: 10.1021/acs.biochem.0c00074). A National Centre for Biological Sciences bioinformatics analysis of NiCo riboswitches in bacteria turned up a subset that were missing key regions necessary for binding cobalt. When Ramesh and her team looked more closely, they noticed that the new riboswitches were embedded in the coding regions of genes related to iron transporters and enzymes—not cobalt-related ones.

The team showed that these riboswitches selectively bind Fe²⁺ in the presence of other metal cations, including cobalt. When the switch binds to Fe²⁺, it changes shape to look like a four-leaf clover, which increases translation of its associated messenger RNA in bacteria.

Now the researchers want to figure out the exact mechanism by which these newly discovered switches increase protein translation. “We propose that there is a portion of the RNA which can recruit ribosomes, and that portion is opened up when iron binds,” Ramesh says.

Ailong Ke, a structural biologist at Cornell University, says the data clearly demonstrate that the switches selectively bind iron, and he says, “That’s very neat.” Ke says this new discovery adds to our fundamental understanding of what RNA can do.

Ramesh’s team will continue to investigate the mechanisms that cause iron-sensing riboswitches to increase translation from their unusual position in the messenger RNA. They are also using the new RNA architecture to develop iron-detecting biosensors.