Bacteria that cause the most diseases, among others Escherichia coli (Pictured here) iron is needed for reproduction. Photo: NIAID.
The cells that make up the different lifestyles of the planet are rich in iron. The atoms of this element help transfer energy molecules, participate in metabolic pathways, and help repair damaged DNA.
Clearly, iron is important. Therefore, it is curious not to know the cellular mechanisms surrounding iron, which are transported between different sub-sites.
Scientists believed that this work was done only by regulatory proteins, and they have studied these proteins well. Recent findings suggest that a different cellular mechanism may also be at work.
A team of scientists from the Bengaluru National Center for Biological Sciences has discovered a new type of reaction in bacteria. This can be linked to iron completely different cellular mechanism.
Riboswitches are RNA entities that detect and respond to levels of different substances within our cells.
Ailong Ke Cornell University structural biologist said c & en the journal said Ramesh & Co.’s research was “very tidy” and that their findings “add to a basic understanding of what RNA can do.”
Arati Ramesh and his team combined bioinformatics and biochemical methods to find this “sensory iron” reaction sticker – what the team calls “Sensei”.
“Iron-binding proteins have been well-studied iron sensors so far. When Sensei RNAs were discovered, the responsibility for iron detection and modulation now extends to RNAs,” said biochemist Ramesh. The World of Chemistry.
Riboswitches are fragments of messenger RNA (mRNA), which is a type of RNA that plays a critical role in the ability of a cell to make proteins using DNA as a guide.
(High school flashback: DNA and RNA are nucleic acids. Carbohydrates, lipids, nucleic acids, and proteins are the four macromolecules that are essential for life).
Riboswitches are part of the process. They instruct the cell by sending “activated” and “turned off” commands that regulate the production of certain proteins.
Supratim Sengupta, a professor at IISER Kolkata and who has previously studied reaction switches that connect to other molecules, said the analogy of a “fuse” is more appropriate than that of a “switch”.
“When a current limit that stops the flow of current in a circuit exceeds a certain limit,” he said, “riboswitches can disrupt the production of certain proteins when the chemical signal – [the presence or quantity of] a small molecule or metal ion – exceeds a certain threshold in the environment “.
For example, fluoride reactors “feel” that many bacteria have high levels of “fluoride” ions. They then respond in a way that increases the expression of other genes in the DNA of bacteria that help bacteria survive better under these conditions.
The simple logic is that the higher the concentration of a particular molecule, the more likely it is to bind to the reactor.
Ramesh and his colleagues were studying reactors that are sensitive to nickel and cobalt or NiCo. They then found a type of NiCo commutator that did not have the necessary characteristics to bind to cobalt.
When they looked closely, they noticed that the root switches were associated with DNA-bound iron transporters and fragments of enzymes.
In the words of Ramesh The World of Chemistry: “These variants were found next to genes encoding iron-bound proteins, increasing the chance of binding to iron.”
To be sure, his team “fed” iron ions into “two” chambers, one with Sensei reactors with mRNA and one without. After some analysis, they concluded that with the mRNA the chamber hijacked a larger amount of iron ions.
Earlier this year, Joseph Cotruvo, Jr., an assistant professor and colleague at Pennsylvania State University, reported in another study that “the riboswitch initially proposed to respond. [NiCo] it also responds to iron. ‘ Later, “we presented data suggesting that iron may actually be the most metallic [this switch] to perceive within a cell, ”he said The Wire Science.
Cotruvo, Jr. explained that the Sensei reactor is closely related to the NiCo reactor but is present in different bacteria. These switches seem to connect iron in different ways – with the effect that the Sensei switch selectively connects to iron.
Scientists have so far found more than 30 types of riboswitches, separated by the molecule that each switch detects. They are mainly found in bacteria. Only a couple of the types are known in higher organisms and none in humans.
Moreover, not all bacteria have the same reactions, and the details of the function are different between different classes of switches.
“It is possible that riboswitches were traces of an early ‘RNA world’ that was the first carrier of RNA genetic information.” [instead of DNA today], and RNA carried out chemical reactions in a cell, most of which catalyze proteins, ”said Cotruvo, Jr.
Riboswitches provides a window for scientists to see how RNA-based organisms, including many pathogenic bacteria, work.
In fact, the peculiarity of the molecules that bind the reaction switches and the importance of these molecules for the survival of the bacterium has led the researcher to investigate the reactor as a new antibiotic target.
“Because iron is an essential nutrient, understanding the way iron reacts are perceived and the specific roles they play in the cell are the first steps in exploring these reactions as potential drug targets,” he added.
The way to do this is to create molecules that mimic riboswitch. According to Sengupta, there could be two ways to do this.
One is to design synthetic reactions that respond to known chemical signals and incorporate them into the genetic material of the pathogen.
The other way is to create small, artificial molecules that mimic the chemical signal that the reactor senses and then activate when the reactor should be tricked to respond by deactivating the production of antibiotic-resistant proteins.
Some researchers are exploring the possibility of building biosensors based on reaction computers. Right now, there is still a lot to learn.
“There’s a lot of effort behind the operation of these rebutters to learn the molecular details and how to adapt the cellular pathways that regulate root switches – learning‘ grammar ’,” said Cotruvo, Jr.
For example, Ramesh et al found that when the Sensei reactor binds to iron (Fe2 + specifically), its shape changes like a four-leaf clover. This transformation affects how mRNA is decoded, which affects the final protein. Ramesh said c & en the next step for his team is to know the biochemical reactions along that path.
“We propose that part of the RNA be a part that can be taken up by ribosomes, and that part opens up when iron binds,” Ramesh told the journal.
This will not be easy. Examining RNA and all of its mechanisms, Cotruvo, Jr. said, poses unique challenges compared to other biological molecules such as DNA and proteins due to the inherent instability and structural plasticity of RNA.
Sengupta agreed. “The SARS-CoV-2 virus is also an RNA virus that we don’t know yet. On the other hand, we know a bit about RNA. … Whether we know enough to handle them effectively is another question. “
Renuka is a science writer in Kulkarni Pune, India and is currently pursuing a PhD in political ecology.