Co-transcriptional DNA and RNA Cleavage during Type III CRISPR-Cas Immunity

Cell. 2015 May 21;161(5):1164-1174. doi: 10.1016/j.cell.2015.04.027. Epub 2015 May 7.


Immune systems must recognize and destroy different pathogens that threaten the host. CRISPR-Cas immune systems protect prokaryotes from viral and plasmid infection utilizing small CRISPR RNAs that are complementary to the invader's genome and specify the targets of RNA-guided Cas nucleases. Type III CRISPR-Cas immunity requires target transcription, and whereas genetic studies demonstrated DNA targeting, in vitro data have shown crRNA-guided RNA cleavage. The molecular mechanism behind these disparate activities is not known. Here, we show that transcription across the targets of the Staphylococcus epidermidis type III-A CRISPR-Cas system results in the cleavage of the target DNA and its transcripts, mediated by independent active sites within the Cas10-Csm ribonucleoprotein effector complex. Immunity against plasmids and DNA viruses requires DNA, but not RNA, cleavage activity. Our studies reveal a highly versatile mechanism of CRISPR immunity that can defend microorganisms against diverse DNA and RNA invaders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Cas Systems*
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • DNA / genetics
  • DNA / metabolism
  • RNA / genetics
  • RNA / metabolism
  • Ribonucleoproteins / metabolism
  • Staphylococcus epidermidis / immunology
  • Staphylococcus epidermidis / metabolism*
  • Staphylococcus epidermidis / virology
  • Transcription, Genetic


  • Ribonucleoproteins
  • RNA
  • DNA