The CRISPR immunity pathway.

<p>CRISPR loci contain clusters of repeats (white boxes) and spacers (colored boxes) that are flanked CRISPR-associated (<i>cas</i>) genes. (<b>A</b>) During adaptation new spacers derived from the genome of the invading virus are incorporated into the CRISPR array by an unknown mechanism. Repeat duplication is also required. (<b>B</b>) During crRNA biogenesis a CRISPR precursor transcript is processed by Cas endoribonucleases within repeat sequences to generate small crRNAs. (<b>C</b>) During targeting the match between the crRNA spacer and target sequences specifies the nucleolytic cleavage of invading mobile genetic elements such as viruses and plasmids. (<b>D</b>) In the CRISPR-Cas system of <i>F. novicida</i>, the tracrRNA (a small RNA mediated in crRNA biogenesis in this system) contains homology to the BLP (bacterial lipoprotein) transcript. The base-pair interaction between the tracrRNA and the BLP mRNA (mediated also by another small RNA, the scaRNA, and the nuclease Cas9) regulates the expression of this immunomodulatory lipoprotein.