RNA-mediated CRISPR-Cas13 inhibition through crRNA structural mimicry

Science. 2025 Apr 25;388(6745):387-391. doi: 10.1126/science.adr3656. Epub 2025 Apr 24.

Abstract

To circumvent CRISPR-Cas immunity, phages express anti-CRISPR factors that inhibit the expression or activities of Cas proteins. Whereas most anti-CRISPRs described to date are proteins, recently described small RNAs called RNA anti-CRISPRs (rAcrs) have sequence homology to CRISPR RNAs (crRNAs) and displace them from cognate Cas nucleases. In this work, we report the discovery of rAcrVIA1-a plasmid-encoded small RNA that inhibits the RNA-targeting CRISPR-Cas13 system in its natural host, Listeria seeligeri. We solved the cryo-electron microscopy structure of the Cas13-rAcr complex, which revealed that rAcrVIA1 adopts a fold nearly identical to crRNA despite sharing negligible sequence similarity. Collectively, our findings expand the diversity of rAcrs and reveal an example of immune antagonism through RNA structural mimicry.

MeSH terms

  • Bacteriophages* / genetics
  • CRISPR-Associated Proteins* / chemistry
  • CRISPR-Associated Proteins* / genetics
  • CRISPR-Cas Systems*
  • Cryoelectron Microscopy
  • Listeria* / genetics
  • Listeria* / virology
  • Molecular Mimicry*
  • Nucleic Acid Conformation
  • Plasmids / genetics
  • RNA, Small Untranslated* / chemistry
  • RNA, Small Untranslated* / genetics
  • RNA, Viral* / chemistry
  • RNA, Viral* / genetics

Substances

  • CRISPR-Associated Proteins
  • RNA, Viral
  • RNA, Small Untranslated