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

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

Author information

1
Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
2
Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: marraffini@rockefeller.edu.

Abstract

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.

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PMID:
25959775
PMCID:
PMC4594840
DOI:
10.1016/j.cell.2015.04.027
[Indexed for MEDLINE]
Free PMC Article

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