CRISPR–Cas: Complex Functional Networks and Multiple Roles beyond Adaptive Immunity

Abstract

CRISPR-Cas is a prokaryotic adaptive immune system that functions by incorporating fragments of foreign DNA into CRISPR arrays. The arrays containing spacers derived from foreign DNA are transcribed, and the transcripts are processed to generate spacer-containing mature CRISPR-RNAs that are employed as guides to specifically recognize and cleave the DNA or RNA of the cognate parasitic genetic elements. The CRISPR-Cas systems show remarkable complexity and diversity of molecular organization and appear to be involved in various cellular functions that are distinct from, even if connected to, adaptive immunity. In this review, we discuss some of such functional links of CRISPR-Cas systems including their effect on horizontal gene transfer that can be either inhibitory or stimulatory, connections between CRISPR-Cas and DNA repair systems as well as programmed cell death and signal transduction mechanisms, and potential role of CRISPR-Cas in transposon integration and plasmid maintenance. The interplay between the primary function of CRISPR-Cas as an adaptive immunity mechanism and these other roles defines the richness of the biological effects of these systems and affects their spread among bacteria and archaea.

The CRISPR-Cas systems were selectively inactivated during evolution of Bacillus cereus group for adaptation to diverse environments

“…2d). Losing the spacer acquisition ability but keeping other components may have some special biological significance for certain strains (164 of 260), since CRISPR-Cas systems have been shown to possess several other unexpected roles beyond its immune function [10]. However, the factors that determined such inactivation pathways of CRISPR-Cas systems in B. cereus group, and the detailed mechanisms and significance involved remain unclear and need further studies.…”

“…The discovery and characterization of CRISPR-Cas, especially in members of Class 2 systems, has led to a revolution in genome editing and engineering technologies [7][8][9]. Beyond its immune function, a number of recent observations revealed unexpected roles for CRISPR-Cas systems in gene expression, autoimmunity, chromosomal segregation or rearrangement, and DNA repairing, although most of the mechanisms involved in these functions still remain unclear [10]. Of particular interest was the discovery of the involvement of CRISPR-Cas systems on the regulation of bacterial virulence [11][12][13].…”

Ecology Shapes Microbial Immune Strategy: Temperature and Oxygen as Determinants of the Incidence of CRISPR Adaptive Immunity

“…Yet others have noted that hot, 33 and possibly other extreme environments can constrain membrane evolution, 34 necessitating the evolution of intracellular defenses like CRISPR or RM sys- 35 tems [16,17,18]. Many have observed that since CRISPR prevents horizontal 36 gene transfer, it may be selected against when such transfers are beneficial (e.g. 37 [19,20]).…”

“…Our data showed a clear interaction between aerobicity and the NHEJ 304 machinery in determining CRISPR incidence that suggests that the link be-305 tween CRISPR and aerobicity may be mediated by the presence of the NHEJ 306 pathway (Fig 4c). The Cas proteins share many structural similarities with 307 proteins implicated in DNA repair, and in some cases prefer to associate with 308 DSBs, and it is perhaps unsurprising that they appear to broadly inhibit the 309 NHEJ pathway whose proteins may be competing for substrate [36].…”

CasLocusAnno: a web-based server for annotating Cas loci and their corresponding (sub)types

“…These systems are the best studied among all the recently discovered bacterial defense weapons (11). Moreover, the functions performed by CRISPR-Cas systems include not only anti-MGE immunity but also the modulation of other biological processes such as gene regulation, bacterial virulence regulation, and DNA repair (12,13).…”