Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25337-5
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Funding
- VENI grant from The Netherlands Organization for Scientific Research (NWO) [016.Veni.171.047]
- TOP grant from The Netherlands Organization for Scientific Research (NWO) [714.015.001]
- VICI grant from The Netherlands Organization for Scientific Research (NWO) [VI.C.182.027]
- Welch Foundation [F-1938]
- National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health (NIH) [R35GM138348]
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation Medical Research Award
- Cancer Prevention and Research Institute of Texas [RR160088]
- Army Research Office [W911NF-19-1-0021]
- David Taylor Excellence Fund in Structural Biology
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Type III CRISPR-Cas systems recognize and cleave target RNAs and produce signalling molecules. Here the authors discover that both processes are governed by a flexible seed region, ultimately resulting in SCOPE, a SARSCoV-2 diagnostic assay with atto-molar sensitivity.
Characteristic properties of type III CRISPR-Cas systems include recognition of target RNA and the subsequent induction of a multifaceted immune response. This involves sequence-specific cleavage of the target RNA and production of cyclic oligoadenylate (cOA) molecules. Here we report that an exposed seed region at the 3 ' end of the crRNA is essential for target RNA binding and cleavage, whereas cOA production requires base pairing at the 5 ' end of the crRNA. Moreover, we uncover that the variation in the size and composition of type III complexes within a single host results in variable seed regions. This may prevent escape by invading genetic elements, while controlling cOA production tightly to prevent unnecessary damage to the host. Lastly, we use these findings to develop a new diagnostic tool, SCOPE, for the specific detection of SARS-CoV-2 from human nasal swab samples, revealing sensitivities in the atto-molar range. Type III CRISPR-Cas systems recognize and cleave target RNAs and produce signalling molecules. Here the authors discover that both processes are governed by a flexible seed region, ultimately resulting in SCOPE, a SARSCoV-2 diagnostic assay with atto-molar sensitivity.
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