Target RNA-Activated CRISPR-Cas12a2 Cuts Nearby DNA More Than RNA

Cas12a2 shows a preference for collateral cleavage of DNA over RNA substrates, even when RNA is more abundant.

• Cas12a2 is the only known CRISPR-associated enzyme that rapidly cleaves three types of nucleic acids: ssRNA, ssDNA, and dsDNA.
• The enzyme preferentially cleaves collateral DNA substrates, indicating a specific substrate preference.
• The cleavage mechanism for dsDNA involves an 'aromatic clamp' that stabilizes unwound and distorted DNA in the active site.
• Cas12a2 can cleave a ssDNA probe in the presence of high concentrations of non-target RNA, unlike Cas13a.
• This study provides insights into the mechanisms and preferences of Cas12a2's collateral cleavage behavior.

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