CoCoNuTs: A diverse subclass of Type IV restriction systems predicted to target RNA

Bell, Ryan T.; Sahakyan, Harutyun; Makarova, Kira S.; Wolf, Yuri I.; Koonin, Eugene V.

doi:10.1101/2023.07.31.551357

PreprintCited by 1CRISPR and Genetic EngineeringBacterial Genetics and BiotechnologyBacteriophages and microbial interactions

CoCoNuTs: A diverse subclass of Type IV restriction systems predicted to target RNA

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Bell, Ryan T., Sahakyan, Harutyun, Makarova, Kira S., Wolf, Yuri I., Koonin, Eugene V.·2023·bioRxiv (Cold Spring Harbor Laboratory)

DOI 10.1101/2023.07.31.551357PMC PMC10542128

Preprint — published as 10.7554/elife.94800.3 · Paper page

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Abstract

A comprehensive census of McrBC systems, among the most common forms of prokaryotic Type IV restriction systems, followed by phylogenetic analysis, reveals their enormous abundance in diverse prokaryotes and a plethora of genomic associations. We focus on a previously uncharacterized branch, which we denote CoCoNuTs ( co iled- co il nu clease tandems) for their salient features: the presence of extensive coiled-coil structures and tandem nucleases. The CoCoNuTs alone show extraordinary variety, with 3 distinct types and multiple subtypes. All CoCoNuTs contain domains predicted to interact with translation system components, such as OB-folds resembling the SmpB protein that binds bacterial transfer-messenger RNA (tmRNA), YTH-like domains that might recognize methylated tmRNA, tRNA, or rRNA, and RNA-binding Hsp70 chaperone homologs, along with RNases, such as HEPN domains, all suggesting that the CoCoNuTs target RNA. Many CoCoNuTs might additionally target DNA, via McrC nuclease homologs. Additional restriction systems, such as Type I RM, BREX, and Druantia Type III, are frequently encoded in the same predicted superoperons. In many of these superoperons, CoCoNuTs are likely regulated by cyclic nucleotides, possibly, RNA fragments with cyclic termini, that bind associated CARF ( C RISPR- A ssociated R ossmann F old) domains. We hypothesize that the CoCoNuTs, together with the ancillary restriction factors, employ an echeloned defense strategy analogous to that of Type III CRISPR-Cas systems, in which an immune response eliminating virus DNA and/or RNA is launched first, but then, if it fails, an abortive infection response leading to PCD/dormancy via host RNA cleavage takes over.

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Discovery of phage defense systems through component modularity networksPreprint
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CoCoNuTs are a diverse subclass of Type IV restriction systems predicted to target RNA
Bell, R. T., Sahakyan, H., Makarova, K. S., Wolf, Y. I., & Koonin, E. V. (2024) · eLife · doi:10.7554/elife.94800.3 · Cited by 3 · see citing works
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Characterization of the Subunits of the McrBC Restriction System in Escherichia Coli K12.
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Type IV-C CRISPR-Cas effector complexes recognize double-stranded DNA and switch on collateral cleavage of ssDNA and RNA
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Authors: Bell, R. T., Sahakyan, H., Makarova, K. S., Wolf, Y. I., & Koonin, E. V.
Affiliations: National Institutes of Health (US)
Corresponding author: Bell, Ryan T.
Koonin, Eugene V.
ORCID: Bell, Ryan T.
Sahakyan, Harutyun
Makarova, Kira S.
Wolf, Yuri I.
Koonin, Eugene V.
Venue: bioRxiv (Cold Spring Harbor Laboratory)
Publisher: openRxiv
Published: 2023-07-31
DOI: 10.1101/2023.07.31.551357
PMC: PMC10542128
OpenAlex: W4385459540
Cited by: 1
References: 109
Citations by year: 2025: 1
Type: posted content
Language: en
Open access: green
doi.org
Licence: cc-by-nc-nd
Locations: bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
PubMed Central (submittedVersion, public-domain)
Funders: Lietuvos Mokslų Akademija
National Institutes of Health (-0001)
University of California, San Francisco
European Regional Development Fund (01.2.2-CPVA-V-716-01-0001)
U.S. National Library of Medicine
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
Keywords: coconut, OB-fold, SmpB, YTH domain, type III CRISPR-Cas, abortive infection, RNA cleavage

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CoCoNuTs: A diverse subclass of Type IV restriction systems predicted to target RNA

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