title: Small CRISPR RNAs guide antiviral defense in prokaryotes.
abstract: Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.
authors.affiliation: Laboratory of Microbiology, Department of Agrotechnology and Food Sciences, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, Netherlands.
authors.forename: Stan J J
authors.initials: SJ
authors.lastname: Brouns
authors.forename: Matthijs M
authors.initials: MM
authors.lastname: Jore
authors.forename: Magnus
authors.initials: M
authors.lastname: Lundgren
authors.forename: Edze R
authors.initials: ER
authors.lastname: Westra
authors.forename: Rik J H
authors.initials: RJ
authors.lastname: Slijkhuis
authors.forename: Ambrosius P L
authors.initials: AP
authors.lastname: Snijders
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Dickman
authors.forename: Kira S
authors.initials: KS
authors.lastname: Makarova
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
authors.forename: John
authors.initials: J
authors.lastname: van der Oost
mesh_terms: D000595:Amino Acid Sequence; D010582:Bacteriophage lambda / Q000235:genetics / Q000254:growth & development; D001483:Base Sequence; D021901:DNA, Intergenic; D004279:DNA, Viral / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D048168:Escherichia coli K12 / Q000235:genetics / Q000378:metabolism / Q000821:virology; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D012322:RNA Precursors / Q000378:metabolism; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D010948:Viral Plaque Assay; D058727:RNA, Small Untranslated
chemical_list: D021901:DNA, Intergenic; D004279:DNA, Viral; D029968:Escherichia coli Proteins; D012322:RNA Precursors; D012329:RNA, Bacterial; D058727:RNA, Small Untranslated