CRISPR-Based Adaptive Immune Systems

The paper introduces CRISPR-Cas systems as small RNA-based defense systems that execute adaptive and heritable immunity against viruses, plasmids, and other mobile genetic elements in archaea and bacteria. The system utilizes CAS proteins, associated with the loci of the CRISPRs in recognizing and destroying the invasive nucleic acids. The components that supply this immunity mediated by CRISPR and how they work are attempted to bring insight by the authors of this paper, mostly in archaea. 

Overview of the CRISPR-Cas Systems

Cas Proteins: There are more than 45 families of cas genes that have been identified with a core set of genes cas1-6 in many organisms. These all form part of the Cas proteins taking part in the different steps of the CRISPR-Cas pathway and are essential for its functioning.

CRISPR-Cas Pathway

Adaptation: In this step, new invader sequences are incorporated into the CRISPR loci. The invading nucleic acid is cut into protospacers that are then inserted into the CRISPR array. PAMs stand for protospacer adjacent motives and are important for invader DNA recognition and its insertion into the CRISPR loci.

crRNA Biogenesis: The process of transcription of CRISPR loci produces precursor crRNAs. Mature individual crRNAs are processed from precursors. Cleavage and processing of pre-crRNAs are associated with Cas proteins, predominantly from the RAMP superfamily.

Invader Silencing: Mature crRNAs guide effector complexes by incorporating them to target and silence invading nucleic acids. Silencing happens either at the DNA or RNA level and is specific to the type of CRISPR-Cas system used.

DNA-Targeting Systems:

This group is comprised of most of the CRISPR-Cas systems, to mention but a few, such as Cse, Csn, and Csm. Such systems employ a mechanism where the crRNAs directly invader DNA cleavage, therefore blocking its replication and proliferation. RNA-Targeting Systems: The Pyrococcus furiosus complex Cmr has the trait of targeting RNA rather than DNA. The complex cleaves complementary RNA sequences guided by crRNAs. 

Diversity and Evolution:

It is summarized that diversity of the CRISPR-Cas systems in prokaryotes exists, including many component variations and mechanisms. Horizontal gene transfer significantly presupposes diffusion of the CRISPR-Cas systems and determines the highly observed level of variation even in closely related species. The co-evolution processes of the CRISPR-Cas systems with their invaders are described, with special regard to the role of PAM sequences and selective pressures exerted.

Conclusion: 

The paper presents the diversity of the CRISPR-Cas systems in different prokaryotes. Several variations of components and mechanisms have been described. The paper highlights that the CRISPR-Cas systems hold the key to prokaryotic immunity and have a significant impact on the formation of evolutionary and ecological features of prokaryotes and their viruses. Still, even for these systems, despite all the breakaways in understanding, serious gaps in knowledge remain at nearly all molecular levels of mechanisms involved in different stages of the CRISPR-Cas pathway.

This paper describes CRISPR-Cas systems as small RNA-based defense systems that confer adaptive and heritable immunity to viruses, plasmids, and other mobile genetic elements acting within archaea and bacteria, involving specific loci termed CRISPR in association with the Cas proteins. It explains the large components and mechanisms of CRISPR-mediated immunity, focusing mostly on archaea.

Reference:

Terns MP, Terns RM. CRISPR-based adaptive immune systems. Curr Opin Microbiol. 2011 Jun;14(3):321-7. doi: 10.1016/j.mib.2011.03.005. Epub 2011 Apr 29. PMID: 21531607; PMCID: PMC3119747.

6/29/2024

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