AsianScientist (Mar. 4, 2021) -Much like Alexander’s Fleming’s serendipitous discovery of penicillin and Yoshizumi Ishino’s chance encounter with CRISPR, researchers from India have reported the discovery of a new class iron-sensing RNA named ‘Sensei RNA’. Their findings were published in Nature Chemical Biology.
While DNA is widely known as the ‘blueprint of life,’ the rise of COVID-19 vaccine makers Moderna and Pfizer-BioNTech has thrust DNA’s lesser-known cousin, RNA, into the spotlight. Aside from bearing relevant genetic information—such as that of SARS-CoV-2, in the vaccines’ case—RNAs are remarkably versatile. Not only can they catalyze biological reactions and finetune gene expression, but RNAs can also act as sensors of various chemical signals.
Over at India’s National Centre for Biological Sciences, graduate students in Dr. Arati Ramesh’s laboratory were examining nickel and cobalt (NiCo)-sensing RNAs in bacteria when they stumbled upon another set of highly similar RNAs. After all, both sets had a distinctive clover leaf-like architecture, with slight differences.
As the team scanned through numerous bacterial genomes, they found that the NiCo-like RNAs were in close proximity to iron-related enzymes and transporters—suggesting that the new set of RNAs could be sensors of iron instead of nickel and cobalt.
To confirm their hypothesis, Ramesh and her team placed the NiCo-like RNAs and iron ions in two different chambers, separated by a membrane that only allowed the iron ions to bleed through. True enough, up to six times more iron ended up in the RNAs’ chamber. When other metal ions were added to the mix, the RNAs only bound iron— proving definitively that the novel RNAs are selective iron sensors.
For the RNAs’ newfound abilities, the researchers fittingly dubbed the new class of molecules Sensei (sense iron) RNAs. When these Sensei RNAs bind iron, they undergo structural changes that trigger adjacent iron-related genes to synthesize proteins.
While the exact function of the Sensei RNA remains to be studied, iron is known to be essential for life—controlling cellular processes including the synthesis of the energy currency ATP. As abnormal levels of iron are toxic to cells, molecules like Sensei RNA provide a useful mechanism for cells to sense iron and react accordingly.
“Particularly, disease-causing pathogenic bacteria need to have the ability to sense iron so that they can be vigilant around heme-rich host tissues [that contain iron],” explained lead author Mr. Siladitya Bandyopadhyay.
Taking their discovery a step further, the team also successfully engineered the Sensei RNA to sense nickel and cobalt in lieu of iron, and vice versa—tweaking the NiCo RNA to instead recognize iron.
“This discovery puts RNAs in the limelight for sensing fundamentally important cellular metabolites like iron,” said Ramesh. “This nanoscale engineering of iron sensing that we demonstrate, will hopefully set the stage for designing iron-biosensors which could be of use to both bacterial biology and biomedicine.”
The article can be found at: Bandyopadhyay et al. (2020) Discovery of Iron-sensing Bacterial Riboswitches.
Source: National Centre for Biological Sciences; Photo: Lam Oi Keat/Asian Scientist Magazine.
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