SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation

Steens JA, Zhu Y, Taylor DW, Bravo JPK, Prinsen SHP, Schoen CD, Keijser BJF, Ossendrijver M, Hofstra LM, Brouns SJJ, Shinkai A, van der Oost J, Staals RHJ. 2021. SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation. Nature Communications. 12, 5033.

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Author
Steens, Jurre A.; Zhu, Yifan; Taylor, David W.; Bravo, JackISTA ; Prinsen, Stijn H. P.; Schoen, Cor D.; Keijser, Bart J. F.; Ossendrijver, Michel; Hofstra, L. Marije; Brouns, Stan J. J.; Shinkai, Akeo; van der Oost, John
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Abstract
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.
Publishing Year
Date Published
2021-08-19
Journal Title
Nature Communications
Volume
12
Article Number
5033
ISSN
IST-REx-ID

Cite this

Steens JA, Zhu Y, Taylor DW, et al. SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation. Nature Communications. 2021;12. doi:10.1038/s41467-021-25337-5
Steens, J. A., Zhu, Y., Taylor, D. W., Bravo, J. P. K., Prinsen, S. H. P., Schoen, C. D., … Staals, R. H. J. (2021). SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-25337-5
Steens, Jurre A., Yifan Zhu, David W. Taylor, Jack Peter Kelly Bravo, Stijn H. P. Prinsen, Cor D. Schoen, Bart J. F. Keijser, et al. “SCOPE Enables Type III CRISPR-Cas Diagnostics Using Flexible Targeting and Stringent CARF Ribonuclease Activation.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-25337-5.
J. A. Steens et al., “SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation,” Nature Communications, vol. 12. Springer Nature, 2021.
Steens JA, Zhu Y, Taylor DW, Bravo JPK, Prinsen SHP, Schoen CD, Keijser BJF, Ossendrijver M, Hofstra LM, Brouns SJJ, Shinkai A, van der Oost J, Staals RHJ. 2021. SCOPE enables type III CRISPR-Cas diagnostics using flexible targeting and stringent CARF ribonuclease activation. Nature Communications. 12, 5033.
Steens, Jurre A., et al. “SCOPE Enables Type III CRISPR-Cas Diagnostics Using Flexible Targeting and Stringent CARF Ribonuclease Activation.” Nature Communications, vol. 12, 5033, Springer Nature, 2021, doi:10.1038/s41467-021-25337-5.
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