Summary information and primary citation
- PDB-id
-
22fn;
DSSR-derived features in text and
JSON formats
- Class
- DNA binding protein
- Method
- cryo-EM (3.17 Å)
- Summary
- cryo-EM structure of ascas12a in complex with crDNA and
RNA target
- Reference
-
Wu X, Lam WH, Zhao Z, Cao Y, Lin H, Feng X, Zhai Y, Hsing
IM (2026): "DNA-guided
CRISPR-Cas12a effectors for programmable RNA recognition
and cleavage." Nat.Biotechnol. doi: 10.1038/s41587-026-03120-5.
- Abstract
- CRISPR-Cas effectors typically rely on RNA guides to
recognize target sequences. In Cas12a, the protospacer
adjacent motif on DNA engages conserved protein residues,
triggering target binding and nuclease activation. Here we
reprogram Cas12a into a DNA-guided, RNA-targeting effector.
Exploiting protospacer-adjacent motif-dependent
interaction, we engineer synthetic CRISPR DNA that engages
Cas12a to form a functional deoxyribonucleoprotein complex,
while repurposing solely RNA as the programmable target.
Structural, biophysical and biochemical analyses reveal the
molecular basis of this DNA-guided, RNA-targeting
configuration and support an activation pathway distinct
from that of canonical RNA-guided systems. DNA-guided
Cas12a enables direct RNA detection and efficient
intracellular RNA knockdown, establishing a modular
activation architecture for CRISPR-Cas12a and expanding the
design space for programmable RNA manipulation.
