Self-targeting by CRISPR: gene regulation or autoimmunity?

Area of Science:

• Microbiology
• Genetics
• Molecular Biology

Background:

• CRISPR (clustered regularly interspaced short palindromic repeats) is a prokaryotic immune system using small RNAs (spacers) to target foreign DNA like phages and plasmids.
• A hypothesis suggests CRISPRs might also regulate host gene expression via self-targeting spacers.

Purpose of the Study:

• To investigate the prevalence and nature of self-targeting spacers within CRISPR systems across diverse organisms.
• To determine if self-targeting represents a regulatory mechanism or an alternative biological phenomenon.

Main Methods:

• Bioinformatic analysis of CRISPR sequences from 330 different organisms.
• Statistical evaluation of self-targeting spacer frequency and conservation.

Main Results:

• Approximately 0.4% (1 in 250) of spacers were found to be self-targeting.
• Self-targeting spacers were identified in 18% of all analyzed CRISPR-bearing organisms.
• Lack of cross-species conservation and presence of degraded repeats near self-targeting spacers were observed.

Conclusions:

• Self-targeting in CRISPR systems appears to be a consequence of autoimmunity rather than a functional gene regulatory mechanism.
• Accidental targeting of self-nucleic acids by CRISPR may impose an autoimmune fitness cost.
• This autoimmune cost could explain the widespread degradation of CRISPR systems observed in prokaryotes.