CRISPR, a new anti-viral system in prokaryotes

We study aspects of the recently discovered anti-viral system in prokaryotes, which might involve RNAi-like mechanism. This system is composed of arrays of regularly interspaced short DNA repeats that are separated by similarly sized non-repetitive spacers. CRISPR arrays, together with a group of associated proteins, confer resistance to phages.

a) Typical structure of a clustered, regularly interspaced short palindromic repeat (CRISPR) locus.

b) CRISPRs acquire phage-derived spacers that provide immunity. Following an attack by a phage, phage nucleic acids proliferate in the cell and new particles are produced, leading to the death of the majority of the sensitive bacteria. A small number of bacteria acquire phage-derived spacers (marked by an asterisk), leading to survival, presumably by CRISPR-mediated degradation of phage mRNA or DNA.

c) Putative, simplified model for CRISPR action. The repeat-spacer array is transcribed into a long RNA, and the repeats assume a secondary structure. Cas proteins recognize the sequence or structure of the repeats and process the RNA to produce small RNAs (sRNAs), each of which contains a spacer and two half repeats. The sRNAs, complexed with additional Cas proteins, base pair with phage nucleic acids, leading to their degradation. Putatively, this process is mediated by one or more of the Cas proteins. CAS, CRISPR-associated.

(Figure taken from Sorek et al., Nature Reviews Microbiology, (2008) 6(3):181-6.)