Translation-dependent degradation of cas12 mRNA triggered by an anti-CRISPR
Nature • • science
Key Points:
- AcrVA2 and its homolog AcrVA2.1 inhibit Cas12a activity and downregulate Cas12a protein expression in various Moraxella bovoculi strains, as shown by phage plaque assays and Western blots.
- Transcriptomic analysis reveals that AcrVA2 significantly reduces mbcas12a mRNA levels compared to controls, indicating mRNA degradation as a mechanism of Cas12a downregulation.
- In vitro assays demonstrate that AcrVA2 does not inhibit or downregulate Cas12a directly, suggesting that its effect on Cas12a requires cellular context or additional factors.
- Fusion of the N-terminal segment of Cas12a to other proteins enables their downregulation by AcrVA2, highlighting the importance of Cas12a's N-terminal amino acids for mRNA degradation.
- AcrVA2 associates with ribosomes and polysomes independently of Cas12a, and RNase E is not required for AcrVA2-mediated cas12a mRNA degradation, indicating a novel mechanism of post-transcriptional regulation.
