Key result
Increasing degrees of tag complementarity suppressed DNA cleavage and cOA synthesis activities, and Cmr3α mutagenesis modulated cOA synthesis depending on tag complementarity.
Why the study?
How extended complementarity between the crRNA 5'-repeat tag and target transcript anti-tag achieves stringent autoimmunity avoidance remained elusive.
The Cmr3 subunit, coupled with the interaction between crRNA tag and anti-tag, functions in facilitating immunity and avoiding autoimmunity in Type III-B CRISPR-Cas systems.
Type III CRISPR-Cas systems code for a multi-subunit ribonucleoprotein (RNP) complex that mediates DNA cleavage and synthesizes cyclic oligoadenylate (cOA) second messenger to confer anti-viral immunity. Both immune activities are to be activated upon binding to target RNA transcripts by their complementarity to crRNA, and autoimmunity avoidance is determined by extended complementarity between the 5ʹ-repeat tag of crRNA and 3ʹ-flanking sequences of target transcripts (anti-tag). However, as to how the strategy could achieve stringent autoimmunity avoidance remained elusive. In this study, we systematically investigated how the complementarity of the crRNA 5ʹ-tag and anti-tag (i.e., tag complementarity) could affect the interference activities (DNA cleavage activity and cOA synthesis activity) of Cmr-α, a type III-B system in Sulfolobus islandicus Rey15A. The results revealed an increasing suppression on both activities by increasing degrees of tag complementarity and a critical function of the 7th nucleotide of crRNA in avoiding autoimmunity. More importantly, mutagenesis of Cmr3α exerts either positive or negative effects on the cOA synthesis activity depending on the degrees of tag complementarity, suggesting that the subunit, coupling with the interaction between crRNA tag and anti-tag, function in facilitating immunity and avoiding autoimmunity in Type III-B systems.
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Guo et al. (2019) studied this question. Mutagenesis of Cmr3α and varying degrees of tag complementarity was evaluated on DNA cleavage activity and cOA synthesis activity. Increasing degrees of tag complementarity suppressed DNA cleavage and cOA synthesis activities, and Cmr3α mutagenesis modulated cOA synthesis depending on tag complementarity.
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