Type III CRISPR Systems

Introduction

Clustered Regularly Spaced Palindromic Repeats (CRISPR)are DNA sequences found throughout prokaryotes and archaea that, in conjunction with a variety of Cas enzymes, are responsible for anti-phage defense mechanisms (Barangou et al, 2007). Generally, foreign bacteriophage DNA is recognized by the enzymes Cas1 and Cas2 and incorporated into the CRISPR array within the host organisms’ genome. These portions of bacteriophage DNA are known as spacers. These spacers can then be transcribed into RNA and used as guides to direct the cleavage of future phage invaders.

There exists a tremendous diversity of CRISPR systems, there are two distinct classes of CRISPR systems each with three types of CRISPR/Cas systems containing their own specialized Cas enzymes and modes of action (Marakova et al, 2017). The type II CRISPR system, encoding a Cas9 endonuclease, is the best characterized of the CRISPR systems due to its prevalence as a gene-editing tool. The discovery and subsequent characterization of type II CRISPR systems and their use in gene editing recently resulted in the Nobel prize being awarded to Jennifer Doudna and Emmanuelle Charpentier (Nobel Prize 2020).

While most CRISPR systems target DNA, type III CRISPR-Cas immunity has been shown to target both DNA and RNA, making them of special interest. Additionally, type III systems are thought to be the most ancient of the CRISPR systems as Cas10, the signature endonuclease of type III systems, was likely the original effector in bacteria and archaea (Markova et al. 2016). Type III CRISPR systems are thought to be the most complex of the CRISPR types, and in the following article I hope to highlight the current knowledge on spacer acquisition, biogenesis, and interference.