New CRISPR element regulates viral defense NatureMicrobiol
. These segments, consisting of alternating repeats and snippets of viral DNA, then produce CRISPR ribonucleic acids . The CRISPR RNAs help the system to recognize and combat viruses. Picking up a viral DNA snippet provides immediate protection. By storing the snippets within the bacterial DNA, protection can be passed on to new generations.
Using the CRISPR-Cas9 system from the pathogen Streptococcus pyogenes as a model, the research team has now discovered that the leader RNA prioritizes immune defense. This sequence is located adjacent to the segment of repeats and viral DNA and is responsible for picking up the viral snippets. During transcription, it folds with the first two repeats surrounding the newest snippet, driving production of the first CRISPR RNA over other CRISPR RNAs.
."The mechanism is specific to many CRISPR systems involving the Cas9 protein commonly used for genome editing, although other mechanisms likely exist for prioritizing anti-viral defense," says Chunyu Liao, lead author of the study published in the journal"This outcome was fully unexpected. The leader RNA was only thought to direct where new viral snippets were integrated," explains corresponding author of the study, Chase Beisel.
"The structure formed between this sequence and the first two repeats is a new element in CRISPR biology. It reveals another mechanism by which RNA can contribute to immune defense. Our research assigns a whole new role to the leader sequence, which has not previously been associated with CRISPR RNA production," adds Liao.
Beyond providing insights into the arms race between bacteria and viruses, this newly discovered mechanism could be used to develop multiplexed CRISPR technologies for the treatment of diseases, which are caused by a variety of mutations in the genome.
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