Abstract
Type III CRISPR-Cas systems, which are widespread in both bacteria and archaea, provide immunity against DNA viruses and plasmids in a transcription-dependent manner. Since an unprecedented cyclic oligoadenylate (cOA) signaling pathway was discovered in type III systems in 2017, the cOA signaling has been extensively studied in recent 3 years, which has expanded our understanding of type III systems immune defense and also its counteraction by viruses. In this review, we summarized recent advances in cOA synthesis, cOA-activated effector protein, cOA signaling-mediated immunoprotection, and cOA signaling inhibition, and highlighted the crosstalk between cOA signaling and other cyclic oligonucleotide-mediated immunity discovered very recently.
Highlights
CRISPR-Cas systems are known to provide adaptive immunity against viruses and plasmids in prokaryotes
A large family of CD-NTases have been found to produce a wide variety of cyclic di- and trinucleotides including 3'3' cyclic UMP-AMP, 3'3'3' cyclic AMP-AMP-GMP, and 2'3'3' cyclic AMP-AMP-AMP, which had never been reported previously (Whiteley et al, 2019; Lowey et al, 2020). These cyclic di- and trinucleotides can activate the downstream effector proteins, such as patatin-like phospholipases, DNA endonucleases, proteases, and pore-forming transmembrane proteins, to mediate anti-phage immunity by abortive infection (Cohen et al, 2019; Lau et al, 2020; Lowey et al, 2020; Ye et al, 2020), which is similar to the action of effector proteins of cyclic oligoadenylate (cOA) signaling in type III systems
COA3-activated DNA endonuclease in cyclic oligonucleotide-based anti-phage signaling system (CBASS) is present in some type III systems and is considered to be an important effector protein of cOA signaling for immunity against phage (Lau et al, 2020; Malone et al, 2020)
Summary
CRISPR-Cas systems are known to provide adaptive immunity against viruses and plasmids in prokaryotes. Based on the composition of effector complexes, CRISPR-Cas systems were divided into two classes which could be further subdivided into six types (types I–VI) and multiple subtypes (Makarova et al, 2020b). Type III effector complex targets both RNA and single-stranded DNA (ssDNA) of the invaders (Tamulaitis et al, 2017). The type III system can be further divided into six subtypes (III A–F), in which Type III-A/D system forms a Csm effector complex composed of five subunits (Csm 1–5) and a single CRISPR RNA (crRNA), while Type III-B/C forms a Cmr effector complex consisting of six subunits (Cmr 1–6) and a crRNA (Makarova et al, 2020b). The crRNA-guided Csm/Cmr complexes recognize the complementary target RNA and cleave it into 6 nt nucleotide intervals using the multiple copies of Csm or Cmr subunit (Hale et al, 2009; Estrella et al, 2016; Kazlauskiene et al, 2016)
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