Recent Breakthrough By NCBS Scientists: A Novel Iron-Sensing Mechanism In Bacteria
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Scientists Discover New Iron-Sensing Riboswitch In Bacteria

All the cells that constitute diverse life forms on Earth have plenty of iron. Normal functioning of DNA repair mechanisms, biological pathways, and even transportation of energy units(ATP) require atoms of iron. Iron undoubtedly plays a major role in our cells, leading us to ponder about various operations carrying iron across the cell and to different organelles.

Until the latest study results, scholars believed that regulatory proteins solely performed cellular mechanisms. New research proposals discuss contributions from other entities as well.

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A new iron-sensing riboswitch in bacteria was discovered by an efficient group of researchers from NCBS(National Centre for Biological Sciences), Bengaluru. This adheres to iron, laying out a clearly distinct molecular mechanism. Riboswitches are specific parts of mRNA that sense and react to cytosolic components.

Cornell University’s structural biologist, Ailong Ke, reported that the findings of Ramesh & Co. are particularly nifty and append to our basic knowledge on RNA functioning, to C&en magazine.

A collaborative study of computational biology and biochemistry lead to the revelation of “Sensei”, the riboswitch, according to Arathi Ramesh and her crew. In compliance with Ramesh’s statement to Chemistry World, iron carrier proteins are the well-studied iron sensors till now. With the breakthrough of Sensei RNAs, regulation plus transportation of iron is now accountable to RNAs.

Riboswitches are one of the messenger RNA (mRNA) components, which is a kind of RNA that codes for protein using a DNA template. Riboswitches play an essential role in regulating the process of translation.

These switches can be more appropriately referred to as fuses, due to its functional resemblance. Riboswitches can effectively halt the translation of particular proteins when certain cell signaling molecules or metal ion surpasses the required level, pointed out by Supratim Sengupta, a lecturer at IISER Kolkata. For instance, fluoride riboswitches in numerous bacteria respond to high levels of fluoride ions, by enhancing the expression of different bacterial genes to cope up with the varying environments.

The basic concept is that if the amount of a particular entity is high, it has a greater possibility of interlinking with riboswitch.

During its nickel and cobalt (NiCo) sensitivity study, Ramesh and her team found a unique NiCo riboswitch that can’t bind to cobalt. Further clarification resulted in observing the relation of riboswitches with DNA associated iron carriers and biocatalysts.

According to Ramesh’s quoting from Chemistry World, these new iron-sensing riboswitch in bacteria were located beside the genes coding for iron-associated proteins, supporting the likelihood of its iron affinity. For confirming this, her team supplied iron ions equally to both compartments with mRNA having Sensei riboswitch and without. After a few experiments, they finalized that the compartment with mRNA had segregated a significant portion of ions.

A few months back, Pennsylvania State University professor, Joseph Cotruvo, Jr. and a coworker had mentioned in The Wire Science about another study that riboswitch was primarily proposed to react to both iron and NiCo. Later on, they implied that iron might be the presumable metal for the riboswitch.

Cotruvo, Jr. discussed that the Sensei riboswitch is very closely associated with the NiCo switch except that it is seen in distinct bacteria. NiCo switches also appear to have a connection with iron whereas the Sensei switch has a sole target, which is iron.

Researchers have uncovered over 30 variants of riboswitches so far, differentiated by the molecule each type senses. They are mainly found in bacteria. Hardly a few kinds are found in higher organisms and not any in humans. Furthermore, not all bacteria have identical riboswitches or similar functions throughout all types of switches.

Cotruvo, Jr. claimed that it is likely that riboswitches are remnants of the ancient RNA period, wherein RNA was the center for genetic information and metabolic activity of the cell, majority of which are now performed by proteins.

Riboswitches provide an advantage to researchers for exploring the working pattern of RNA-centred organisms, particularly pathogenic bacteria. Indeed, the uniqueness of riboswitches for their exclusive binding strategies to certain molecules, and the value of those molecules for the existence of the microorganism, has encouraged scientists to discover riboswitches as unique antibiotic targets as well. Since iron is a vital nutrient, comprehending how iron-sensing riboswitches work as well as their detailed duties in the cell are the primary stages toward experimenting with these riboswitches as prospective drug-targets, he added.

The method to do this is to produce molecules that imitate riboswitch. According to Sengupta, there might be two means to do this. One is to create artificial riboswitches that respond to familiar chemical signals and include them right into the hereditary product of the microorganism. The alternative method is to create tiny, synthetic molecules that imitate the chemical signal which riboswitch detects, and after that deceive it to get activated when it should not, making riboswitch react by turning off the manufacturing of proteins responsible for antibiotic resistance.

Some scientists are also discovering the possibility of creating biosensors based upon riboswitches. However today, there is still much to uncover.

There is also a great deal of initiative in finding out the molecular facts behind how these riboswitches function, and also exactly how the riboswitches manage metabolic pathways, said Cotruvo, Jr.

For instance, Ramesh and others detected that when the Sensei riboswitch attaches to iron, its configurations changes to mimic a four-leaf clover. This influences how the mRNA is translated, which consequently affects the protein. Ramesh informed C&en that her group’s next step is to identify the biochemical stages in this pathway. They recommend that there is a section of the RNA that can recruit ribosomes, which is opened up when iron binds, Ramesh stated in the magazine.

This won’t be easy. Researching RNA and all its devices, in Cotruvo, Jr.’s saying, has distinct difficulties in comparison with other biomolecules like DNA and also proteins because of RNA’s innate labile nature and structural plasticity.

Sengupta agreed that even the COVID-19 virus is an RNA virus regarding which we are unaware. Conversely, we are aware of RNA.  Whether we understand to efficiently control them is a different issue altogether.

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 Author : Geema George