Abstract

Prokaryotes have evolved several defence mechanisms to protect themselves from viral predators. Clustered regularly interspaced short palindromic repeats (CRISPR) and their associated proteins (Cas) display a prokaryotic adaptive immune system that memorizes previous infections by integrating short sequences of invading genomes—termed spacers—into the CRISPR locus. The spacers interspaced with repeats are expressed as small guide CRISPR RNAs (crRNAs) that are employed by Cas proteins to target invaders sequence-specifically upon a reoccurring infection. The ability of the minimal CRISPR-Cas9 system to target DNA sequences using programmable RNAs has opened new avenues in genome editing in a broad range of cells and organisms with high potential in therapeutical applications. While numerous scientific studies have shed light on the biochemical processes behind CRISPR-Cas systems, several aspects of the immunity steps, however, still lack sufficient understanding. This review summarizes major discoveries in the CRISPR-Cas field, discusses the role of CRISPR-Cas in prokaryotic immunity and other physiological properties, and describes applications of the system as a DNA editing technology and antimicrobial agent.This article is part of the themed issue ‘The new bacteriology’.

Highlights

  • Being the most abundant entities on our planet, bacterial and archaeal viruses display a constant threat to prokaryotic life

  • This review seeks to summarize the major discoveries made in the field of Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, and describes the biological roles of the system in antiviral defence and other biological pathways as well as its significance for medical application

  • CRISPR-Cas comprises a genomic locus called CRISPR that harbours short repetitive elements separated by unique sequences, which can originate from mobile genetic elements (MGEs) such as bacteriophages, transposons or plasmids

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Summary

Introduction

Being the most abundant entities on our planet, bacterial and archaeal viruses (bacteriophages or phages) display a constant threat to prokaryotic life. In a process called priming, the interference machinery of several type I CRISPR-Cas systems can stimulate the increased uptake of new spacers upon crRNA-guided binding to a protospacer that was selected upon a first infection [19,25,30]. This process displays a distinct adaptation mode compared to naive spacer acquisition as it strictly requires a pre-existing spacer matching the target. Type V-A, only employ crRNA for target localization and degradation [28,29]

Anti-CRISPR mechanisms
Beyond adaptive immunity
Significance and applications
Perspectives
Makarova KS et al 2015 An updated evolutionary
54. Brouns SJ et al 2008 Small CRISPR RNAs guide
88. Louwen R et al 2013 A novel link between
Findings
A CRISPR with roles in Myxococcus xanthus
Full Text
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