To replicate information, life tends to have pretty simple ways of doing things. To copy DNA, DNA is generally used as a template. To make RNA, cells generally use DNA as a template, while the RNA, in turn, provides the instructions for making proteins. But now a bacteria has revealed a different path, and it’s deeply surprising. In one half of this newly discovered system, a protein acts as a molecular template to build a specific repeating DNA sequence, essentially allowing the information written in the amino acids to determine the information written in the DNA. And that’s the other way around: a bit like using a cake as a template to write a recipe, rather than using a recipe as a template to make one. “Instead of copying one strand of DNA to form the other, as occurs in normal DNA replication, the system uses two different reverse transcriptases to independently generate the two complementary strands,” biochemist Samuel Sternberg of Columbia University told ScienceAlert. “One enzyme copies an RNA template, while the other uses amino acids in the protein itself to determine which DNA building blocks are added. The two resulting DNA strands then meet and pair to produce double-stranded DNA, ultimately helping bacteria defend against viruses.” The structure of DNA, showing how its two strands are linked by complementary base pairs: A with T, and C with G. (National Human Genome Research Institute)DNA is basically the system storage of life information. Its famous double helix structure consists of two strands built from four chemical bases: adenine (A), cytosine (C), guanine (G) and thymine (T). These four ingredients constitute the genetic material of all living beings. However, they cannot be combined in any way. They are paired according to specific rules: A with T and C with G. This means that the sequence of each strand will contain the information necessary to build the other. When a cell replicates DNA, it separates the two strands like a zipper, with each strand acting as a template to build the new strand that wraps around it. A string whose sequence says AGCT, for example, will obviously require the sequence TCGA. In some cases, enzymes called reverse transcriptases can produce DNA using RNA as a template; that’s a trick that retroviruses use, for example. But either way, a nucleic acid is involved in the process. That’s where bacteria get a little weird, Sternberg and his colleagues discovered. These organisms are known to use a system called defense-associated reverse transcriptases (DRT) as part of their immune response against viruses, but it was unclear how this system actually works. Escherichia coli bacteria, which use an arsenal of molecular defenses against invading viruses. (Science Photo Library/Getty Images) Sternberg and his colleagues studied one such system, called DRT3, in Escherichia coli, using a series of experiments to determine what its two reverse transcriptases were doing. When they examined the structure of one of those enzymes, DRT3b, using cryo-electron microscopy, they found something they didn’t expect. “We knew from our experiments that DRT3b could produce this very specific repetitive DNA sequence without the RNA that the other reverse transcriptase requires. But we didn’t know how it did it,” Sternberg said. “The real ‘aha’ moment came from biochemical experiments and the cryo-EM structure. Hiroshi Nishimasu and his team were able to see the DNA product in the enzyme, and the structure placed these two amino acids in exactly the right positions to explain the alternating sequence. “That immediately suggested a rather far-fetched possibility: the protein itself was specifying the sequence. “However, the structure alone was not enough to prove it. They altered the two amino acids they suspected were responsible for specifying the sequence. When they did, both DNA synthesis and the bacteria’s antiviral defense broke down, confirming that the amino acids were critical to the process. More surprisingly, DRT3b was doing this without any nucleic acid template. Instead, the two amino acids placed next to the active site of the enzyme effectively acted as a template: one favored the incorporation of A and the other C. The repeat DNA strand produced by DRT3b, as revealed by cryo-electron microscopy, the enzyme uses amino acids in the protein itself to determine the alternating CACA sequence (Wang et al., Cell, 2026). It’s only half of what DRT3 is doing. The DRT3b protein-templated DNA strand is only one of two strands created by the system. A second reverse transcriptase, DRT3a, independently constructs another repeating strand of DNA, but this time, in the more conventional way, using RNA as a template. The two chains are complementary. Once formed, they spontaneously encounter each other and pair, forming the well-known double-stranded double helix. DNA. This is also backwards from the usual way of doing things. Normally, the two strands of DNA do not form independently: an existing strand provides the template for its new partner. In this case, neither of the newly created threads provides instructions for the other. One gets its sequence information from the RNA, the other from the protein, and only then do they join together. We think that one strand carries the information necessary to form the other. Here, the two strands are synthesized independently, using two completely different types of templates (RNA for one and protein for the other) and only then joined together to form a double helix. “To me, that’s a pretty remarkable example of how inventive evolution can be with very familiar molecular building blocks.” The DRT3 defense system in action. (Wang et al., Cell, 2026) But DRT3 doesn’t perform this elaborate molecular trick just for show. It’s a defense system, and the strange DNA appears to act as a kind of booby trap for invading viruses. Under normal conditions, an enzyme called RecBCD continually destroys the DNA produced by DRT3, preventing it from accumulating. RecBCD is itself part of the bacteria’s defenses and helps destroy invading viral DNA. Some viruses, as part of their attack toolkit, produce proteins that disable RecBCD. “The virus is trying to disable RecBCD because RecBCD itself is an important antiviral defense,” Sternberg explained. “But by disabling it, the virus inadvertently removes the DRT3 brake.” Related: Your DNA is not just a double helix. Scientists have just discovered what else it hides. As the DNA produced by DRT3 builds up, the bacteria stops growing, which in turn prevents the virus from replicating efficiently. The bacterial cell is sacrificed to prevent the virus from spreading to the surrounding population. More research is needed to determine how DRT3 stops the growth of the bacteria. The researchers are also interested in investigating whether similar systems are capable of writing different DNA sequences. “My suspicion is that this is the tip of the iceberg,” Sternberg said. “I doubt that DRT3b is the only enzyme capable of this type of unconventional DNA synthesis. It remains to be seen if there are many other proteins that use exactly this amino acid template mechanism, but I would be surprised if nature only invented it once.” “The findings were published in Cell. This article was fact-checked by Fiona MacDonald and edited by Fiona MacDonald. While we take pride in our process, we are only human. If you spot an error, please let us know.
