Journal
SCIENCE
Volume 321, Issue 5891, Pages 960-964Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1159689
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Funding
- Intramural NIH HHS [Z01 LM000061-14] Funding Source: Medline
- Engineering and Physical Sciences Research Council [EP/D033713/1, EP/E036252/1] Funding Source: researchfish
- EPSRC [EP/D033713/1, EP/E036252/1] Funding Source: UKRI
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Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats ( CRISPRs). Here we show how virus- derived sequences contained in CRISPRs are used by CRISPR- associated ( Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus- derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.
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