Science: Reveals a new CRISPR system that targets only RNA
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In a new study, from the National Institutes of Health (NIH), Harvard University - Massachusetts Institute of Technology Broad Institute (Brode Institute), Massachusetts Institute of Technology, Rutgers University Researchers at the Langsway campus and in Russia's Skolkovo Institute of Technology have described a new CRISPR system that targets RNA rather than DNA. The results of the study were published online in the journal Science on June 2, 2016, and the paper titled "C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector".
This new CRISPR system has the potential to provide a powerful method for cell manipulation. Although DNA editing allows for permanent changes in the cell's genome, this CRISPR-based RNA targeting approach may allow scientists to make cellular genomes subject to temporary changes that can be adjusted up and down as needed, and are larger than existing RNA interference methods. Specificity and functionality.
In this study, Feng Zhang from the Broad Institute and colleagues with Eugene Koonin from NIH and colleagues, Konstantin Severinov from Rutgers University's New Brunswick campus A team that identified an RNA-directed enzyme, C2c2, capable of targeting and degrading RNA, and functionally described C2c2.
These findings revealed that the first naturally occurring CRISPR-only CRISPR system identified by C2c2- was discovered by this cooperative group in October 2015 to help protect bacteria from viral infections. They confirmed that C2c2 can be programmed to cleave specific RNA sequences in bacterial cells, which may add an important tool to the molecular biology toolbox.
C2c2 acts only on RNA and can be an important complement to the CRISPR-Cas9 system that targets DNA. This ability to target only RNA—helping to execute genomic instructions—allows people to manipulate RNA specifically and with high throughput, and to manipulate gene function more widely. This has the potential to accelerate the pace of understanding, treating and preventing disease.
"C2c2 opens the door to a whole new area of ​​powerful CRISPR tools. It has a lot of possibilities for C2c2, and we are excited to develop it for life science research and medicine," said Feng Zhang, co-author of the paper. Platform."
"The study of C2c2 reveals a new biological mechanism that bacteria seem to be used against viral infections. The application of this strategy may be very compelling," said Eugene Koonin, co-author of the paper.
Currently, the most common technique used to perform gene knockdown (also translated as gene knockdown) is small interfering RNA (siRNA). According to the researchers, the C2c2 RNA editing method shows better specificity and potential for a wider range of applications, such as:
(1) Adding nucleotide components to specific RNA sequences to alter their function - how they are translated into proteins, which will make them valuable tools for large-scale screening and construction of synthetic regulatory networks. ;
(2) Fluorescent labeling of RNA with C2c2 to study their transport and subcellular localization.
In this new study, researchers were able to use C2c2 to precisely target binding and removal of specific RNA sequences, which reduced the level of expression of the protein produced by the RNA. This suggests that C2c2 may be an alternative to siRNA, to compensate for the specificity and simplicity of CRISPR-based DNA editing methods, and to enable scientists to use RNA to carry out regulated gene knockdown.
C2c2 has the advantage of making it suitable for tool development: (1) C2c2 is a two-component system that requires only a single-guide RNA to function; (2) C2c2 is genetically-encoded, which means the necessary group The fraction can be synthesized as DNA and transported into tissues and cells.
Zhang Clab graduate student Omar Abudayyeh said, "C2c2 may have the greatest impact on our understanding of RNA in disease and cell function."
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