title: Co-transcriptional DNA and RNA Cleavage during Type III CRISPR-Cas Immunity.
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.
authors.affiliation: Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Poulami
authors.initials: P
authors.lastname: Samai
authors.affiliation: Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Pyenson
authors.affiliation: Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Goldberg
authors.affiliation: Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Asma
authors.initials: A
authors.lastname: Hatoum-Aslan
authors.affiliation: Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: marraffini@rockefeller.edu.
authors.forename: Luciano A
authors.initials: LA
authors.lastname: Marraffini
mesh_terms: D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004247:DNA / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D013212:Staphylococcus epidermidis / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D014158:Transcription, Genetic
chemical_list: D012261:Ribonucleoproteins; D012313:RNA; D004247:DNA