This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A new antiviral defense system discovered by Columbia scientists could be adapted in the future into a gene editor that slows down aging in our cells and improves cancer therapies. At the same time, the discovery also sheds light on an ancient event in evolution that may have helped set the stage for the emergence of higher organisms.
The newly discovered system, called DRT10 (for Defense-Associated Reverse Transcriptase 10), protects bacteria from viruses, like the CRISPR antiviral system discovered decades ago that has since unleashed a new era of genome engineering. But unlike CRISPR, which works by cutting DNA, DRT10 employs a reverse transcriptase, an enzyme that gives it the power to manufacture DNA within the cell. "It's a very exotic system that departs from the typical way we think about genome engineering," says Samuel Sternberg, professor of biochemistry and molecular biophysics at Columbia University Vagelos College of Physicians and Surgeons, investigator with the Howard Hughes Medical Institute and the study's senior author.
"Instead of cutting DNA like CRISPR, or swapping one letter of genetic code like base editors, this system uses RNA as a template to write new sequences of DNA. That gives us a different starting point for building tools to engineer cells." The story of DRT10's discovery and a first look at its mechanisms were published today in a paper in Nature, which also reveals a likely and surprising relationship between the bacterial defense system and telomerase, an enzyme needed by nearly all higher organisms to replenish telomeres—the protective stretches of DNA at the ends of our chromosomes. "This is a powerful example of how basic research can illuminate deep questions about aging, cancer and the evolution of life," says Sternberg.
"Studying how bacteria defend themselves against viruses has revealed an unexpected connection to one of the most consequential enzymes in human biology." The Sternberg lab is known for searching the genomes of bacteria and archaea for the inventive methods these age-old organisms possess to control and sometimes alter their genomes. One group of bacterial DNA-writing enzymes—aptly named the "Unknown Group" back in 2008—grabbed the lab's attention for its dozens of reverse transcriptases with still-unknown functions. Because reverse transcription creates new DNA from strands of RNA, the enzymes are considered promising starting points for creating new gene-editing tools to write new therapeutic sequences into the genome.
"We had this large family of enzymes that could write DNA, but almost no idea what bacteria were using them for," says Sternberg. "That was an irresistible biological mystery with the potential to yield entirely new biotechnology tools." Stephen Tang, a graduate student in the lab, found DRT10 in that group and discovered that DRT10 uses its reverse transcriptase to fight viruses by creating a long piece of DNA with a repetitive sequence read from a template RNA. Tang worked alongside fellow co-first authors Josephine L.
Ramirez and Qixiang He and an international team, with Ramirez leading the biochemical studies and He and Israel S. Fernández leading the structural work that revealed how DRT10's protein and RNA components fit together. As Tang dug deeper to understand how the reverse transcriptase operates, he realized that the enzyme works a lot like telomerase—a reverse transcriptase found in an evolutionarily distant group of organisms: us.
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