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18 HEALTH AND LABORATORY MAGAZINE

MICROBES’ MYSTERY DNA HELPS

DEFEAT VIRUSES AND HAS GENOME

EDITING POTENTIAL

Seven years ago, an far has appeared only as a genes used to fight off protein—to defeat a variety
understanding of nature preprint, reports a similar phages. Such genes tend of viruses.
inspired a revolutionary finding. to be close to one another,
new technology, when and his team developed For a retron called Ec48,
researchers turned a The new understanding of a computer program that Sorek and colleagues
defense system used by retrons’ natural function searched for new defense showed the associated
bacteria to thwart viruses could boost efforts to put systems next to the genes protein delivers the coup
into the gene-editing tool them to work. Retrons are for the CRISPR and other de grâce by homing in
now known as CRISPR. But “quite efficient tools for known antiviral constructs. on a bacterium’s outer
for another emerging gene accurate and efficient ge- One stretch of DNA stood membrane and altering its
editor the understanding nome editing,” says Rotem out to Weizmann gradu- permeability. The research-
has lagged the applica- Sorek, a microbial genom- ate student Adi Millman ers concluded that the
tions. For several years, icist at the Weizmann
researchers have been Institute of Science and an
adapting retrons—myste- author of the Cell study. But
rious complexes of DNA, they don’t rival CRISPR yet,
RNA, and protein found in part because the tech-
in some bacteria—into a nology hasn’t been made
potentially powerful way to to work in mammalian cells.
alter genomes of single cell
organisms. Now, biology is In the 1980s, researchers
catching up, as two groups studying a soil bacterium
were puzzled to find many
copies of short sequenc-
es of single-stranded
DNA littering the cells.
Sparking thoughts of CRISPR’s The mystery deepened
beginnings, the genetic elements when they learned each because it included a gene retron somehow “guards”
bit of DNA was attached
called retrons can only edit single- to an RNA with a comple- for a reverse transcriptase another molecular complex
cell organisms so far. mentary base sequence. flanked by stretches of that is the bacterium’s first
DNA that didn’t code for
line of antiviral defense.
Eventually they realized
an enzyme called re- any known bacterial pro- Some phages deactivate
verse transcriptase had teins. By chance, she came the complex, which triggers
report evidence that, like made that DNA from the across a paper about the retron to unleash the
CRISPR, retrons are part attached RNA, and that retrons and realized that membrane-destroying
of the bacterial immune all three molecules—RNA, the mysterious sequences protein and kill the infected
arsenal, protecting the mi- DNA, and enzyme—formed encoded one of their RNA cell, Millman, Sorek, and
crobes from viruses called a complex. components. “That was a their team reported on 6
phages. nontrivial leap,” Sorek says. November in Cell.
Similar constructs, dubbed
Last week in Cell, one team retrons for the reverse The team then noticed that A second group has
described how a specific transcriptase, were found in the DNA encoding retron reached similar conclu-
retron defends bacteria, many bacteria. “They really components often accom- sions. Led by Athanasios
triggering newly infected are a remarkable biological panied a protein-coding Typas, a microbiologist at
cells to self-destruct so the entity, yet nobody knew gene, and the protein var- the European Molecular Bi-
virus can’t replicate and what they were for,” says ied from retron to retron. ology Laboratory (EMBL),
spread to others. The Cell Ilya Finkelstein, a biophys- The team decided to test Heidelberg, the group
paper “is the first to con- icist at the University of its hunch that the cluster realized that next to the
cretely determine a natural Texas, Austin. of sequences represent- genes coding for a retron
function for retrons,” says ed a new phage defense. in a Salmonella bacterium
Anna Simon, a synthetic Sorek came upon an early They went on to show that was a gene for a protein
biologist at Strand Ther- hint of their function when bacteria needed all three toxic to Salmonella. The
apeutics who has studied he and his colleagues components—reverse tran- team discovered the retron
the bacterial oddities. searched through 38,000 scriptase, the DNA-RNA normally keeps the toxin
Another paper, which so bacterial genomes for hybrid, and the second under wraps, but activates