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Cas12a3 Uncovered: CRISPR Nuclease That Precisely Cleaves tRNA Tails

Researchers detail the structural basis for tail cleavage in a Nature paper with potential diagnostic applications.

Overview

  • The peer-reviewed study, published January 7, 2026 in Nature, comes from teams at the Helmholtz institutes, Utah State University, and European partners.
  • Cas12a3 uses an RNA guide to recognize foreign RNA, then undergoes a conformational change to bind and cut the conserved 3′ tail of tRNAs, shutting down protein synthesis.
  • The mechanism halts viral protein production while sparing host DNA, contrasting with Cas12a2’s broad collateral nucleic-acid cleavage described as its polar opposite.
  • Cryo-EM analysis revealed a unique tRNA loading domain that positions the tRNA 3′ tail for precise cleavage.
  • The researchers demonstrated a laboratory proof of concept that combined Cas12a3 with two other nucleases to simultaneously detect RNAs from SARS-CoV-2, influenza, and RSV, which is not yet a clinical test.