Co-transcriptional DNA and RNA cleavage during type III CRISPR-cas immunity

Poulami Samai, Nora Pyenson, Wenyan Jiang, Gregory W. Goldberg, Asma Hatoum-Aslan, Luciano A. Marraffini

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1164-1174
Number of pages11
JournalCell
Volume161
Issue number5
DOIs
StatePublished - May 30 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Samai, P., Pyenson, N., Jiang, W., Goldberg, G. W., Hatoum-Aslan, A., & Marraffini, L. A. (2015). Co-transcriptional DNA and RNA cleavage during type III CRISPR-cas immunity. Cell, 161(5), 1164-1174. https://doi.org/10.1016/j.cell.2015.04.027