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Scoop.it!
Researchers from Utah State University and Germany’s Helmholtz Institute for RNA-based Infection Research demonstrate that upon recognition of an RNA target, Cas12a2 cleaves all the other nucleic acids present, destroying the bacterial cell and preventing bacteriophage from replicating. 
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Scoop.it!
Bacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1,2. Several RNA-targeting CRISPR–Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases3–5. However, a CRISPR-mediated abortive mechanism that leverages indiscriminate DNase activity of an RNA-guided single-effector nuclease has yet to be observed. Here we report that RNA targeting by the type V single-effector nuclease Cas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA (dsDNA). After recognizing an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and dsDNA. Within cells, the activation of Cas12a2 induces an SOS DNA-damage response and impairs growth, preventing the dissemination of the invader. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided RNA-targeting tool. These findings expand the known defensive abilities of CRISPR–Cas systems and create additional opportunities for CRISPR technologies. RNA targeting by the Sulfuricurvum type V single-effector nuclease SuCas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA—after recognition of an RNA target through an activating protospacer-flanking sequence, SuCas12a2 efficiently degrades ssRNA, ssDNA and dsDNA.
BigField GEG Tech's insight:
Scientists at the Helmholtz Institute Würzburg in Germany, and Benson Hill, Inc. (Missouri) and Utah State University in the U.S., have found a nuclease, which they dubbed Cas12a2, that represents an entirely new type of CRISPR immune defense. Unlike any other previously known nuclease of the CRISPR-Cas immune system, the source of ‘gene scissors,’ Cas12a2 destroys DNA to shut down an infected cell. The findings could lead to new CRISPR technologies for molecular biology diagnostics, among other applications.
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Despite its phylogenetic placement with DNA-targeting nucleases, Cas12a2 targets and cleaves RNA. When researchers put Cas12a2 in test tubes with pure DNA and a guide, nothing happened, because its target was not present and it remained inactive. However, sometimes a small amount of activating RNA was present, contaminating the sample. When the RNA was present and Cas12a2 recognized its target, it destroyed all nucleic acids in the tube. Unlike the CRISPR-Cas9 system, when Cas12a2 finds its target, the infected cell(s) die. This mechanism is known as abortive infection. One of the obvious applications of Cas12a2 is in CRISPR diagnostics. It can easily be reprogrammed to detect certain targets, such as RNA viruses, with high specificity. The researchers have already demonstrated the feasibility of this approach in their recent work. Cas12a2 could also be programmed to kill specific cell types, such as tumor cells, for therapeutic purposes.