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Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity

CRISPR-Cas systems are a family of adaptive immune systems that use small CRISPR RNAs (crRNAs) and CRISPR-associated (Cas) nucleases to protect prokaryotes from invading plasmids and viruses (i.e., phages). Type III systems launch a multilayered immune response that relies upon both Cas and non-Cas...

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Autores principales: Chou-Zheng, Lucy, Hatoum-Aslan, Asma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762709/
https://www.ncbi.nlm.nih.gov/pubmed/36479971
http://dx.doi.org/10.7554/eLife.81897
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author Chou-Zheng, Lucy
Hatoum-Aslan, Asma
author_facet Chou-Zheng, Lucy
Hatoum-Aslan, Asma
author_sort Chou-Zheng, Lucy
collection PubMed
description CRISPR-Cas systems are a family of adaptive immune systems that use small CRISPR RNAs (crRNAs) and CRISPR-associated (Cas) nucleases to protect prokaryotes from invading plasmids and viruses (i.e., phages). Type III systems launch a multilayered immune response that relies upon both Cas and non-Cas cellular nucleases, and although the functions of Cas components have been well described, the identities and roles of non-Cas participants remain poorly understood. Previously, we showed that the type III-A CRISPR-Cas system in Staphylococcus epidermidis employs two degradosome-associated nucleases, PNPase and RNase J2, to promote crRNA maturation and eliminate invading nucleic acids (Chou-Zheng and Hatoum-Aslan, 2019). Here, we identify RNase R as a third ‘housekeeping’ nuclease critical for immunity. We show that RNase R works in concert with PNPase to complete crRNA maturation and identify specific interactions with Csm5, a member of the type III effector complex, which facilitate nuclease recruitment/stimulation. Furthermore, we demonstrate that RNase R and PNPase are required to maintain robust anti-plasmid immunity, particularly when targeted transcripts are sparse. Altogether, our findings expand the known repertoire of accessory nucleases required for type III immunity and highlight the remarkable capacity of these systems to interface with diverse cellular pathways to ensure successful defense.
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spelling pubmed-97627092022-12-20 Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity Chou-Zheng, Lucy Hatoum-Aslan, Asma eLife Microbiology and Infectious Disease CRISPR-Cas systems are a family of adaptive immune systems that use small CRISPR RNAs (crRNAs) and CRISPR-associated (Cas) nucleases to protect prokaryotes from invading plasmids and viruses (i.e., phages). Type III systems launch a multilayered immune response that relies upon both Cas and non-Cas cellular nucleases, and although the functions of Cas components have been well described, the identities and roles of non-Cas participants remain poorly understood. Previously, we showed that the type III-A CRISPR-Cas system in Staphylococcus epidermidis employs two degradosome-associated nucleases, PNPase and RNase J2, to promote crRNA maturation and eliminate invading nucleic acids (Chou-Zheng and Hatoum-Aslan, 2019). Here, we identify RNase R as a third ‘housekeeping’ nuclease critical for immunity. We show that RNase R works in concert with PNPase to complete crRNA maturation and identify specific interactions with Csm5, a member of the type III effector complex, which facilitate nuclease recruitment/stimulation. Furthermore, we demonstrate that RNase R and PNPase are required to maintain robust anti-plasmid immunity, particularly when targeted transcripts are sparse. Altogether, our findings expand the known repertoire of accessory nucleases required for type III immunity and highlight the remarkable capacity of these systems to interface with diverse cellular pathways to ensure successful defense. eLife Sciences Publications, Ltd 2022-12-08 /pmc/articles/PMC9762709/ /pubmed/36479971 http://dx.doi.org/10.7554/eLife.81897 Text en © 2022, Chou-Zheng and Hatoum-Aslan https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Microbiology and Infectious Disease
Chou-Zheng, Lucy
Hatoum-Aslan, Asma
Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity
title Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity
title_full Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity
title_fullStr Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity
title_full_unstemmed Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity
title_short Critical roles for ‘housekeeping’ nucleases in type III CRISPR-Cas immunity
title_sort critical roles for ‘housekeeping’ nucleases in type iii crispr-cas immunity
topic Microbiology and Infectious Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9762709/
https://www.ncbi.nlm.nih.gov/pubmed/36479971
http://dx.doi.org/10.7554/eLife.81897
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