The CRISPR-Cas system in prokaryotes protects against viruses and other genome invaders. This system consists of clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins. Researchers identified a CRISPR-Cas effector complex composed of small invader-targeting RNAs (psiRNAs) and RAMP module (Cmr) Cas proteins. These complexes cleave complementary target RNAs at a fixed distance from the 3' end of the psiRNAs. In Pyrococcus furiosus, psiRNAs exist in two size forms with a common 5' sequence tag but distinct 3' ends that direct cleavage of a given target RNA at two distinct sites. The results indicate that prokaryotes possess a unique RNA silencing system that functions by homology-dependent cleavage of invader RNAs. The CRISPR-Cas system is hypothesized to use CRISPR-derived RNAs to guide Cas proteins to silence potential genome invaders. CRISPR loci are found in nearly all sequenced archaeal genomes and approximately half of bacterial genomes. Cas genes are found in the genomes of prokaryotes that possess CRISPRs. Over 40 Cas genes have been described, a subset of which is found in any given organism. The proteins encoded by the Cas genes include predicted RNA binding proteins, endo- and exo-nucleases, helicases, and polymerases. Recent studies have demonstrated that CRISPRs and Cas genes function in invader defense in prokaryotes. RNAs from the CRISPR loci are hypothesized to guide the CRISPR-Cas defense response based on their potential to base pair with invading nucleic acids. Available data indicate that entire CRISPR loci are transcribed from the leader region, producing primary transcripts containing the full set of CRISPR repeats and embedded invader-derived sequences. These large precursor RNAs are processed into shorter intermediate RNAs by Cas endonucleases. However, the ultimate products of the CRISPR loci appear to be smaller RNAs. In Pyrococcus furiosus, the most abundant CRISPR RNAs are two species of ~45 nucleotides and ~39 nucleotides. These small, abundant products of the CRISPR loci are thought to be the prokaryotic silencing (psi)RNAs of the CRISPR-Cas RNA silencing pathway. The CRISPR-Cas system is hypothesized to use CRISPR-derived RNAs to guide Cas proteins to silence potential genome invaders. CRISPR loci are found in nearly all sequenced archaeal genomes and approximately half of bacterial genomes. Cas genes are found in the genomes of prokaryotes that possess CRISPRs. Over 40 Cas genes have been described, a subset of which is foundThe CRISPR-Cas system in prokaryotes protects against viruses and other genome invaders. This system consists of clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins. Researchers identified a CRISPR-Cas effector complex composed of small invader-targeting RNAs (psiRNAs) and RAMP module (Cmr) Cas proteins. These complexes cleave complementary target RNAs at a fixed distance from the 3' end of the psiRNAs. In Pyrococcus furiosus, psiRNAs exist in two size forms with a common 5' sequence tag but distinct 3' ends that direct cleavage of a given target RNA at two distinct sites. The results indicate that prokaryotes possess a unique RNA silencing system that functions by homology-dependent cleavage of invader RNAs. The CRISPR-Cas system is hypothesized to use CRISPR-derived RNAs to guide Cas proteins to silence potential genome invaders. CRISPR loci are found in nearly all sequenced archaeal genomes and approximately half of bacterial genomes. Cas genes are found in the genomes of prokaryotes that possess CRISPRs. Over 40 Cas genes have been described, a subset of which is found in any given organism. The proteins encoded by the Cas genes include predicted RNA binding proteins, endo- and exo-nucleases, helicases, and polymerases. Recent studies have demonstrated that CRISPRs and Cas genes function in invader defense in prokaryotes. RNAs from the CRISPR loci are hypothesized to guide the CRISPR-Cas defense response based on their potential to base pair with invading nucleic acids. Available data indicate that entire CRISPR loci are transcribed from the leader region, producing primary transcripts containing the full set of CRISPR repeats and embedded invader-derived sequences. These large precursor RNAs are processed into shorter intermediate RNAs by Cas endonucleases. However, the ultimate products of the CRISPR loci appear to be smaller RNAs. In Pyrococcus furiosus, the most abundant CRISPR RNAs are two species of ~45 nucleotides and ~39 nucleotides. These small, abundant products of the CRISPR loci are thought to be the prokaryotic silencing (psi)RNAs of the CRISPR-Cas RNA silencing pathway. The CRISPR-Cas system is hypothesized to use CRISPR-derived RNAs to guide Cas proteins to silence potential genome invaders. CRISPR loci are found in nearly all sequenced archaeal genomes and approximately half of bacterial genomes. Cas genes are found in the genomes of prokaryotes that possess CRISPRs. Over 40 Cas genes have been described, a subset of which is found