Evidence map›Paper›PMID 42700392›Full record

ArticleCell reports2026

Type IV-C CRISPR-Cas effector complexes recognize double-stranded DNA and switch on collateral cleavage of ssDNA and RNA.

Conor C Pittman, Chengtao Xu, Ryan J Catchpole, Sandra Garrett, Ryan Fuchs, Xiaomeng Chu, Kira S Makarova, Eugene V Koonin, Peng Zhao, Lance Wells and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Conor C PittmanDepartment of Microbiology, University of Georgia, Athens, GA 30605, USA.
Chengtao XuDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Ryan J CatchpoleDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30605, USA.
Sandra GarrettDepartment of Genetics and Genome Sciences, University of Connecticut, Farmington, CT 06030, USA.
Ryan FuchsRNA Division, New England Biolabs, Ipswich, MA 01938, USA.
Xiaomeng ChuDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA.
Kira S MakarovaComputational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Eugene V KooninComputational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Peng ZhaoDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30605, USA.
Lance WellsDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30605, USA.
Brenton R GraveleyDepartment of Genetics and Genome Sciences, University of Connecticut, Farmington, CT 06030, USA.
Ailong KeDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. Electronic address: ailong.ke@yale.edu.
Michael P TernsDepartment of Microbiology, University of Georgia, Athens, GA 30605, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30605, USA; Department of Genetics, University of Georgia, Athens, GA 30605, USA. Electronic address: mterns@uga.edu.

Funding

Genomic Analysis of Nucleic Acid TransactionsR35GM118140 · NIGMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI GRAVELEY, BRENTON R. · 2016 to 2025
$6.8M
CRISPR Capture, Destroy, and Counter-Attack MechanismsR35GM118160 · NIGMS · UNIVERSITY OF GEORGIA · PI TERNS, MICHAEL P · 2016 to 2025
$5.8M
NIGMS NIH HHS R35 GM118140NIGMS NIH HHS R35 GM118160
6 · The paper itself

Abstract

Type IV-C CRISPR-Cas systems remain enigmatic compared to other class 1 systems. Here, we expand the type IV-C catalog, identifying two phylogenetically distinct clades primarily found in archaea (IV-C1) or bacteria (IV-C2), distinguishable by the Cas10IVc subunit architecture. We functionally and structurally characterize type IV-C1 systems from Thermococcus onnurineus (Ton) and Pyrococcus abyssi (Pab). Type IV-C complexes assemble with crRNAs derived from distinct CRISPR arrays and recognize a 5'-GGG-3' protospacer adjacent motif (PAM) to bind double-stranded DNA targets. Target recognition activates the HD domain of Cas10IVc, triggering metal-dependent collateral cleavage of single-stranded DNA and RNA. This behavior is explained by allosteric alignment of the HD active site, triggered by PAM-dependent R-loop formation, as revealed by cryo-EM. Together, our findings suggest that type IV-C systems provide immunity via non-specific cleavage of nucleic acids generated during mobile genetic element replication or transcription.

Indexed as

CRISPR-Associated ProteinsCRISPR-Cas SystemsDNA, Single-StrandedRNAPyrococcus abyssiThermococcusCRISPR-Associated ProteinsDNA, Single-StrandedRNAadaptive immunityCas10collateral cleavageCP: molecular biologyCRISPR-Cas systemsThermococcalestype IV-C CRISPR

Identifiers

PMID42700392
PMCPMC13676074

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.