Metagenomic discovery of CRISPR-associated transposons

Proc Natl Acad Sci U S A. 2021 Dec 7;118(49):e2112279118. doi: 10.1073/pnas.2112279118.


CRISPR-associated Tn7 transposons (CASTs) co-opt cas genes for RNA-guided transposition. CASTs are exceedingly rare in genomic databases; recent surveys have reported Tn7-like transposons that co-opt Type I-F, I-B, and V-K CRISPR effectors. Here, we expand the diversity of reported CAST systems via a bioinformatic search of metagenomic databases. We discover architectures for all known CASTs, including arrangements of the Cascade effectors, target homing modalities, and minimal V-K systems. We also describe families of CASTs that have co-opted the Type I-C and Type IV CRISPR-Cas systems. Our search for non-Tn7 CASTs identifies putative candidates that include a nuclease dead Cas12. These systems shed light on how CRISPR systems have coevolved with transposases and expand the programmable gene-editing toolkit.

Keywords: CAST; CRISPR RNA; bioinformatics; gene editing; transposition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • CRISPR-Associated Proteins / metabolism
  • CRISPR-Cas Systems / genetics
  • CRISPR-Cas Systems / physiology
  • Clustered Regularly Interspaced Short Palindromic Repeats / genetics*
  • Clustered Regularly Interspaced Short Palindromic Repeats / physiology
  • DNA Transposable Elements / genetics*
  • DNA Transposable Elements / physiology
  • Endonucleases / genetics
  • Gene Editing
  • Metagenome
  • Metagenomics / methods
  • RNA, Guide, CRISPR-Cas Systems / genetics
  • Transposases / genetics


  • Bacterial Proteins
  • CRISPR-Associated Proteins
  • DNA Transposable Elements
  • RNA, Guide, CRISPR-Cas Systems
  • Transposases
  • Endonucleases