As you read this story, you will learn the following:
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Although the functions of codons (combinations of three nucleotides) may vary, the long-standing rule is that each codon has a specific purpose.
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However, new evidence suggests that a microorganism sometimes uses the codon UGA as a stop codon and sometimes uses it to encode the amino acid pyrrolysine.
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The discovery of this “loose” translation could help scientists better understand the archaea in our bodies and improve the treatment of disease.
The building blocks of life are formed by a simple process: DNA is transcribed into RNA, which then becomes protein. All life follows the same instructions for protein formation, instructions based on 61 codons composed of three nucleotides, all of which are combinations of the four nucleic acids adenine (A), cytosine (C), guanine (G) and uracil (U).
These codons are usually assigned to one of the 20 canonical amino acids or a so-called stop codon (usually UAA, UAG, or UGA), which sends a signal to terminate protein building and release the polypeptide chain. For decades, scientists have argued that this process needed to be precise to avoid imprecision in the genetic code. However, a new study published in diary Proceedings of the National Academy of Sciences (PNAS) Led by scientists at the University of California (UC) Berkeley, at least one species of archaea, a microorganism called a methanogen, has been discovered Methanosarcina acetatesurvives by using a more “loose” approach to translation.
“Objectively, ambiguity in the genetic code should be harmful; you end up generating random libraries of proteins,” Dipti Nayak, senior author of the paper at UC Berkeley, said in a press statement. “But biological systems are more ambiguous than we thought, and this ambiguity is actually a feature, not a bug.”
Scientists speculate that this “ambiguity” allows microbes to introduce the unusual amino acid pyrrolysine to produce enzymes that break down certain foods. Although life varies in terms of number of amino acids and codon coding (some codons are even redundant), one thing is generally OK: A codon has only one meaning. That is, until now.
Pyrrolysine is widely present in methanogenic archaea, and the study’s lead author Katie Shalvarjian, now a postdoctoral fellow at Lawrence Livermore National Laboratory, noticed while studying these methanogens that, curiously, the UAG codon Mycobacterium acetivorus Not always interpreted as pyrrolysine.
“The UAG codon is like a fork in the road that can be interpreted as a stop codon or a pyrrolysine residue,” Shalvarjian said in a press statement.
“They go back and forth between whether they should stop or whether they should add this new amino acid to keep going,” Nayak added. “They can’t decide. They just do both, and they seem to solve the problem by making this random choice.”
Preliminary findings suggest that archaeal selection was not completely random. When cells are flooded with amino acids, microorganisms tend to interpret UAG as integrated pyrrolysine and convert it into the appropriate protein. However, when there are fewer surrounding proteins, UAG often acts as a stop codon, resulting in a completely different protein.
This research connects to the future of human health in surprising ways. For example, the body relies on archaea to remove methylamine and keep the liver healthy, so it’s important to understand this ambiguity in their molecular mechanisms. Additionally, scientists could try to introduce similar levels of imprecision into gene therapies, which could address diseases caused by premature stop codons (such as cystic fibrosis).
“This really opens the door to finding interesting ways to control how cells interpret stop codons,” Nayak said.
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