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    Home > Biochemistry News > Microbiology News > The new progress of Xiang Hua/Li Ming's team reveals the mystery of the origin of CRISPR-Cas "guard RNA"

    The new progress of Xiang Hua/Li Ming's team reveals the mystery of the origin of CRISPR-Cas "guard RNA"

    • Last Update: 2021-10-10
    • Source: Internet
    • Author: User
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    The popular "genetic cut" CRISPR-Cas9 originated from the study of a special immune system in microorganisms (the CRISPR-Cas system) by scientists
    .

    CRISPR-Cas is widely distributed in bacteria and archaea, and can generate adaptive immunity to genetic elements such as viruses and plasmids
    .

    When a foreign virus invades, the Cas protein can obtain a specific DNA sequence from the virus and insert it into the CRISPR structure to form a new spacer unit, forming a permanent "memory" of the invading virus
    .

    The sequence containing the new spacer is transcribed and processed to produce mature crRNA, which can guide the Cas protein to specifically degrade the virus that invades again, thereby protecting the host cell as an adaptive immune system
    .

    However, the CRISPR-Cas system will also cause fitness costs to host cells in the long-term evolution process, such as the risk of self-immunity, hindering the acquisition of foreign beneficial genes, etc.
    , resulting in frequent loss of CRISPR-Cas
    .

    Therefore, how the CRISPR-Cas system can exist widely in microorganisms (exist in about 90% of archaea and 50% of bacteria) and function is an important scientific problem that has long plagued scientists
    .

    In April of this year, the team from the Institute of Microbiology of the Chinese Academy of Sciences to Hua/Li Ming reported in the internationally renowned academic journal "Science" a new type of double RNA-type toxin-antitoxin system CreTA (CRISPR- regulated Toxin-Antitoxin), which answers this important scientific question for the first time and reveals its ingenious molecular mechanism
    .

    Soon, the origin of the "Guard RNA System" (CreTA) and its significance in biological evolution aroused the attention of the academic community
    .

    Professor Jim Maher, a member of the American Association for the Advancement of Science, believes that the details revealed by the study are very interesting and compelling, especially the discovery of the "selfish" property of CRISPR coupled toxin-antitoxin, which indicates that the CRISPR immune system will punish inadvertent discards during evolution.
    Their host is a good textbook material (recommended by "Faculty Opinions")
    .

    On August 8, Dr.
    Scott W Roy, a genetic and evolutionary scholar, focused on this important discovery and published a special review in Trends in Microbiology.
    He believed that the study provided a fascinating understanding of the evolutionary mechanism of selfish genes in biological complexity.
    Example: The discovery of a new toxin-antitoxin system (TA) system based on RNA and dependent on the Cas protein will stimulate people to re-understand and explore the diversity of the TA system, and these “addictions” or “addictions” in a broader sense How to protect genetic elements and promote the evolution of new cell functions in biological evolution will be an important new proposition for "selfish" elements
    .

    Recently, the Xiang Hua/Li Ming team reported their latest research progress in the internationally renowned academic journal Nucleic Acids Research, revealing the evolutionary origin of the CreTA system-derived from the highly degraded and alienated mini-CRISPR structure
    .

    The team systematically analyzed CreTA of a large number of bacteria and archaea and found that most of the antitoxin gene creA has two CRISPR repeat-like sequences.
    Interestingly, these two repeats are highly degraded and have large differences in sequence, which makes creA Genes are difficult to discover and predict, and it is difficult to define them as mini-CRISPR structures
    .

    However, through a combination of genetic experiments and high-throughput sequencing technology, they confirmed that these degraded repeats still retain the key bases for Cas6 nuclease recognition and processing.
    Therefore, most CreA RNAs have almost the same molecular architecture as crRNA.
    (Fixed length 5'-handle and 3'-handle), thus revealing the evolutionary origin of the CreTA system highly degraded from mini-CRISPR (Figure 1)
    .

    This discovery will also provide important clues and new parameters for the systematic prediction and analysis of CreTA
    .

    Figure 1.
    The evolution model from mini-CRISPR to creA (Nucleic Acids Research, doi: 10.
    1093/nar/gkab821).
    In this latest study, the team also discovered a type of cytotoxicity by hijacking rare isoleucine tRNA The new CreT RNA
    .

    This new toxin has the same mini-ORF with two consecutive rare codons and a conserved stem-loop structure like the Salina spp.
    CreT reported in their Science work
    .

    Interestingly, by replacing the two isoleucine codons of the former with the arginine codons carried by the latter, its targeting can be modified so that it can hijack the rare arginine tRNA and cause cytotoxicity
    .

    Therefore, the team believes that suppressing cell activity by hijacking specific rare tRNAs is a convergence strategy for many CreT RNA-type toxins, which will provide important elements and new ideas for molecular tool development and genetic engineering applications
    .

    The above research results were published online in Nucleic Acids Research on September 22, 2021.
    PhD student Cheng Feiyue at the State Key Laboratory of Microbial Resources Preliminary Development of the Institute of Microbiology, Chinese Academy of Sciences, Yu Haiying, an engineer, and Wang Rui, an associate professor of Chengdu Medical College, contributed to the paper The co-first authors, Li Ming and Xiang Hua of the Institute of Microbiology are the 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, and the Youth Innovation Promotion Association of the Chinese Academy of Sciences
    .

    Related literature: Cheng F, Wang R, Yu H, Liu C, Yang J, Xiang H, Li M.
    Divergent degeneration of creA antitoxin genes from minimal CRISPRs and the convergent strategy of tRNA-sequestering CreT toxins.
    Nucleic Acids Res.
    2021 Sep 22:gkab821.
    doi: 10.
    1093/nar/gkab821.
    Epub ahead of print.
    PMID: 34551428.
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