Regulation of CRISPR–Cas adaptive immune systems

Abstract

CRISPR–Cas systems are prokaryotic immune systems that allow defense against invasion by foreign genetic elements. Through the acquisition of genetic memory representing prior exposure, the CRISPR–Cas machinery identifies complementary nucleic acids and mediates their destruction. Since their discovery, CRISPR–Cas research has exploded, with major progress into their mechanism and biotechnological application. In contrast, we are only beginning to understand how CRISPR–Cas activity is regulated. Recent studies have uncovered both conserved regulatory pathways, in addition to more specific mechanisms. Identifying the stimuli linking invasion with CRISPR–Cas activation will be essential in unraveling their ecological roles, evolutionary success and might offer strategies to control immunity for particular applications. We highlight factors impinging on CRISPR–Cas regulation across diverse bacterial and archaeal species.