This research explores a newly discovered bacterial defense mechanism where the CRISPR–Cas12a3 system provides immunity by specifically targeting and cleaving tRNA tails. While many immune systems disable viral replication by destroying viral genomes, this variant is unique because it preferentially inactivates host tRNAs after recognizing a viral target. By removing the essential 3′ CCA tail of tRNAs not currently engaged in translation, the nuclease triggers a global translational shutdown that halts cellular growth to stop the infection. Structural analysis reveals that Cas12a3 has evolved specialized domains that allow it to distinguish these small RNA molecules from other types of RNA. This discovery identifies a previously unknown adaptive immune strategy in bacteria that utilizes programmable tRNA degradation to resist phage attacks. The findings highlight the hyper-evolvable nature of Cas12 enzymes, which can be repurposed by evolution to strike diverse molecular targets beyond traditional DNA or mRNA.

References:

• Dmytrenko O, Yuan B, Crosby K T, et al. RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity[J]. Nature, 2026: 1-10.