While codons (combinations of three nucleotides) may vary in their functions, an old rule held that each codon has a specific purpose. However, new evidence suggests that a microbe sometimes uses the UGA codon as a stop codon and sometimes uses it to code for the amino acid pyrilose. This discovery can help scientists to better understand the archaea in the human body and improve the treatment of diseases.
The building blocks of life are formed by a simple process: DNA is transcribed into RNA, which is then converted into protein. And all living things follow the same instructions for forming proteins; Instructions are based on 61 codons, each of which is made of three nucleotides and is a combination of four nucleic acids: adenine (A), cytosine (C), guanine (G) and uracil (U).
These codons are usually assigned to one of the standard 20 amino acids or to a stop codon (usually UAA, UAG, or UGA), which sends a signal to terminate protein synthesis and release the polypeptide chain. For decades, scientists assumed that this process had to be precise to avoid faulty genetic code.
However, a new study published in the Proceedings of the National Academy of Sciences (PNAS) by scientists from the University of California, Berkeley, shows that at least one archaea, the methane-producing microbe Methanosarcina acetivorans, survives by using a special translation method.
“Objectively, ambiguity in the genetic code should be harmful,” Dipti Nayak, one of the authors of the paper, said in a statement. You end up generating a random set of proteins. “But biological systems are more complex than we imagine, and this ambiguity is actually a feature, not a defect.”
Scientists hypothesize that this “ambiguity” allows the microbe to import the rare amino acid pyrilose and produce enzymes that break down certain foods. Although life varies in the number of amino acids and which codons code for which amino acids, one thing is usually certain: a codon has only one meaning.
Pyrilosine is widespread in methane-producing archaea, and the study’s lead author, Kathy Shalvarjian, noticed while studying these methanogenic organisms that strangely the UAG codon in M. acetivorans was not always interpreted as pyrrolosine. “The UAG codon is like a crossroads, where it can either be interpreted as a stop codon or as a pyrrolosine residue,” Shalvarjian said.
“They’re oscillating between seeing this as an end codon or going ahead with adding this new amino acid,” Nayak said. They cannot decide. “They just do both and seem to be okay with making that random choice.” Preliminary findings suggest that the selection of archae is not entirely random. When the amino acid is abundant in the cell, the microbe tends to interpret the UAG as integrated pyrilosine and convert it into the appropriate protein. However, when the amount is less, UAG often acts as a stop codon, resulting in a completely different protein.
This research is unexpectedly related to the future of human health. For example, the human body relies on archaea to remove methylamines and maintain liver health, so understanding this ambiguity in its molecular machinery is important. Additionally, scientists can experiment with introducing a similar level of imprecision into gene therapies that can address problems caused by premature termination codons (such as cystic fibrosis). “This discovery really opens the door to finding interesting ways to control how cells interpret stop codons,” says Nayak.
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