TY - JOUR
T1 - Co-transcriptional DNA and RNA cleavage during type III CRISPR-cas immunity
AU - Samai, Poulami
AU - Pyenson, Nora
AU - Jiang, Wenyan
AU - Goldberg, Gregory W.
AU - Hatoum-Aslan, Asma
AU - Marraffini, Luciano A.
N1 - Funding Information:
We are grateful to Seth Darst, Arkady Mustaev, and Brian Bae for providing CBR703 and help with transcription inhibition assays. We also like to thank Andrew Varble for critical reading of the manuscript. P.S. is supported by a Helmsley Postdoctoral Fellowship for Basic and Translational Research on Disorders of the Digestive System at The Rockefeller University. L.A.M. is supported by the Searle Scholars Program, Rita Allen Scholars Program, an Irma T. Hirschl Award, a Sinsheimer Foundation Award and a NIH Director’s New Innovator Award (1DP2AI104556-01).
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/5/30
Y1 - 2015/5/30
N2 - 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.
AB - 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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U2 - 10.1016/j.cell.2015.04.027
DO - 10.1016/j.cell.2015.04.027
M3 - Article
C2 - 25959775
AN - SCOPUS:84930085853
SN - 0092-8674
VL - 161
SP - 1164
EP - 1174
JO - Cell
JF - Cell
IS - 5
ER -