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Regulation of cyclic oligoadenylate synthesis by the Staphylococcus epidermidis Cas10-Csm complex

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dc.contributor.authorNasef, Mohamed
dc.contributor.authorMuffly, Mary C.
dc.contributor.authorBeckman, Andrew B.
dc.contributor.authorRowe, Sebastian J.
dc.contributor.authorWalker, Forrest C.
dc.contributor.authorHatoum-Aslan, Asma
dc.contributor.authorDunkle, Jack A.
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.date.accessioned2023-09-28T19:14:57Z
dc.date.available2023-09-28T19:14:57Z
dc.date.issued2019
dc.description.abstractCRISPR-Cas systems are a class of adaptive immune systems in prokaryotes that use small CRISPR RNAs (crRNAs) in conjunction with CRISPR-associated (Cas) nucleases to recognize and degrade foreign nucleic acids. Recent studies have revealed that Type III CRISPR-Cas systems synthesize second messenger molecules previously unknown to exist in prokaryotes, cyclic oligoadenylates (cOA). These molecules activate the Csm6 nuclease to promote RNA degradation and may also coordinate additional cellular responses to foreign nucleic acids. Although cOA production has been reconstituted and characterized for a few bacterial and archaeal Type III systems, cOA generation and its regulation have not been explored for the Staphylococcus epidermidis Type III-A CRISPR-Cas system, a longstanding model for CRISPR-Cas function. Here, we demonstrate that this system performs Mg2+-dependent synthesis of 3-6 nt cOA. We show that activation of cOA synthesis is perturbed by single nucleotide mismatches between the crRNA and target RNA at discrete positions, and that synthesis is antagonized by Csm3-mediated target RNA cleavage. Altogether, our results establish the requirements for cOA production in a model Type III CRISPR-Cas system and suggest a natural mechanism to dampen immunity once the foreign RNA is destroyed.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationNasef, M., Muffly, M. C., Beckman, A. B., Rowe, S. J., Walker, F. C., Hatoum-Aslan, A., & Dunkle, J. A. (2019). Regulation of cyclic oligoadenylate synthesis by the Staphylococcus epidermidis Cas10-Csm complex. In RNA (Vol. 25, Issue 8, pp. 948–962). Cold Spring Harbor Laboratory. https://doi.org/10.1261/rna.070417.119
dc.identifier.doi10.1261/rna.070417.119
dc.identifier.orcidhttps://orcid.org/0000-0001-6252-0587
dc.identifier.orcidhttps://orcid.org/0000-0002-0937-1524
dc.identifier.orcidhttps://orcid.org/0000-0003-4503-8734
dc.identifier.orcidhttps://orcid.org/0000-0003-2395-8900
dc.identifier.orcidhttps://orcid.org/0000-0003-2056-6311
dc.identifier.urihttps://ir.ua.edu/handle/123456789/11166
dc.languageEnglish
dc.language.isoen_US
dc.publisherCold Spring Harbor Lab Press
dc.rights.licenseAttribution-NonCommercial 4.0 International (CC BY-NC 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectCRISPR-Cas
dc.subjectCas10
dc.subjectcrRNA
dc.subjectinterference
dc.subjectoligoadenylate
dc.subjectGUIDED SURVEILLANCE COMPLEX
dc.subjectCRISPR RNA
dc.subjectCRYSTAL-STRUCTURE
dc.subjectANTIVIRAL DEFENSE
dc.subjectDNA CLEAVAGE
dc.subjectIMMUNITY
dc.subjectINTERFERENCE
dc.subjectDEGRADATION
dc.subjectSYSTEM
dc.subjectCLASSIFICATION
dc.subjectBiochemistry & Molecular Biology
dc.titleRegulation of cyclic oligoadenylate synthesis by the Staphylococcus epidermidis Cas10-Csm complexen_US
dc.typeArticle
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