The retron switch: Researchers develop approach to leverage the function of an elusive small satellite DNA molecule and to harness its immune defense powers

The retron switch: Researchers develop approach to leverage the function of an elusive small satellite DNA molecule and to harness its immune defense powers

Since first discovered in the 1980s, retrons have puzzled researchers who simply wanted to know what these bacterial DNA sequences actually did. Now, EMBL scientists have identified that some retrons encode toxin proteins, which they keep inactive with the help of a small DNA fragment. When a bacterial virus (phage) attacks bacteria, the small DNA can sense the attack and unleash the toxin.

“Bacterial chromosomes contain hundreds of different toxin/antitoxin systems of unknown function that might be leveraged to inhibit phages, and our findings provide an approach to understand how they could do that,” said Nassos Typas, a group leader in the Genome Biology Unit and a co-chair of EMBL’s Microbial Ecosystems and Infection Biology transversal themes. His group has just reported its latest findings in Nature.

Simply put, retrons contain an enzyme called reverse transcriptase that uses small RNA as a template to produce multicopy single-stranded DNA (msDNA). Although scientists knew how this msDNA is produced across many bacteria, its function and role in the cell had remained enigmatic until June 2020, when the Typas group, as well as the Sorek group from the Weizmann Institute of Science in Israel, posted their independent studies in an open-access preprint repository.

“For more than 30 years, we’d had no clue why bacteria have retrons because no phenotypes had been associated with cells lacking retrons or msDNA,” said Jacob Bobonis, the paper’s lead author, who completed his PhD in the Typas group.

But new information came to light when a previous member of the Typas group found an important clue — a phenotype. They discovered that a pathogenic bacterium Salmonella cannot grow in colder temperatures without making msDNA. The group then teamed up with the lab of Helene Andrews-Polymenis at Texas A&M University and her then postdoc, Johanna Elfenbein, now PI at the University of Madison. Together, they identified that Salmonella cells unable to make msDNA were also sensitive to a lack of oxygen, preventing them from colonising a cow’s gut.

While these phenotypes alone didn’t show the retrons’ special immune defence capabilities, they gave the scientists a starting point to study the retrons further.

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