Uncover the unique evolutionary path of CRISPR guardian RNA

The Xiang Hua/Li Ming research team at the Institute of Microbiology of the Chinese Academy of Sciences previously discovered a new class of double-RNA toxin-antitoxin system CreTA (Science, 2021) that can guard CRISPR-Cas, and further research found that CreTA originated from the mini-CRISPR structure, but its repeat sequence repeat was highly degraded (Nucleic Acids Res, 2021).

Why CreTA's repeat sequence undergoes this degradation, and what the evolutionary drivers are, scientists don't know
.
Recently, Li Ming's team and Xiang Hua's team reported the latest research progress
on this issue at Nucleic Acids Research.

Through a large number of genetic experiments, the research team found that CreA can only use the CRISPR-Cas system carrying this CreTA element to inhibit the transcriptional expression of CreT toxin and form a "cell addiction" circuit, but cannot use the CRISPR-Cas system
of the close relative.
As a result, each CRISPR-Cas gene cluster has evolved its own unique guard RNA, which may have facilitated the deep differentiation and diversification of the CRISPR-Cas system (Figures 1A and B
).
Through evolutionary analysis, the authors found that although the two repeating components of CreA underwent serious sequence conservatism, the degradation of the first repeat(ΨR1) was more severe, and by modifying the repeat component, the adaptability of
CreTA to the close CRISPR-Cas system could be greatly improved.
In addition, the degenerated repeat sequence helps maintain the stability of CreTA, which the authors used for CRISPR gene editing, significantly improving the stability and editing efficiency of CRISPR tools (Figure 1C
).

This study elaborates the unique evolutionary path of CreTA to achieve "functional evolution" through "sequence degradation", reveals its self-stability improvement through repeat degradation, and highly specifically protects the molecular mechanism of CRISPR-Cas gene clusters in its vicinity, and provides new components and new ideas
for the innovative upgrade of CRISPR tools.

The study, published online at Nucleic Acids Research on August 26, 2022, was cited by the judges as making an important contribution to the field and an important proof of principle
for innovation in multiple CRISPR technologies 。 Li Ming's team postdoctoral Cheng Feiyue, master student Wu Aici and doctoral student Liu Chao are the first co-authors of the paper, and researchers Li Ming and Xiang Hua are co-corresponding authors
of the paper.
The research was supported by the National Natural Science Foundation of China, the Strategic Pilot Research Program of the Chinese Academy of Sciences, the Youth Innovation Promotion Association of the Chinese Academy of Sciences, and the Postdoctoral Innovation Talent Support Program
.

Full-text links:

　　https://academic.
oup.
com/nar/advance-article-abstract/doi/10.
1093/nar/gkac712/6677323