Evidence map›Paper›PMID 28722012›Full record

ArticleNature2017

Type III CRISPR-Cas systems produce cyclic oligoadenylate second messengers.

Ole Niewoehner, Carmela Garcia-Doval, Jakob T Rostøl, Christian Berk, Frank Schwede, Laurent Bigler, Jonathan Hall, Luciano A Marraffini, Martin Jinek

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 282 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
282citing papers in PubMed, 1 pooled it
–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

282 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Engineering CRISPR guide RNAs for programmable RNA sensors.Biochemical Society transactions · 2023
    Pooled it
  2. CRISPR/Cas Systems: Biological Basis and Genome Editing Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. Article
  4. Molecular control of bacterial immunity.Nature structural & molecular biology · 2026
    Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Structural mechanism of SAM-AMP and SAM-AMPNature communications · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

222 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Ole NiewoehnerDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Carmela Garcia-DovalDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Jakob T RostølLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065-6399, USA.
Christian BerkDepartment of Chemistry and Applied Biosciences, Institute for Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
Frank SchwedeBIOLOG Life Science Institute GmbH, Flughafendamm 9a, D-28199 Bremen, Germany.
Laurent BiglerDepartment of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Jonathan HallDepartment of Chemistry and Applied Biosciences, Institute for Pharmaceutical Sciences, Vladimir-Prelog-Weg 1-5/10, 8093 Zurich, Switzerland.
Luciano A MarraffiniLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065-6399, USA.
Martin JinekDepartment of Biochemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.

Funding

Howard Hughes Medical InstituteNIH HHS 1DP2AI104556-01
6 · The paper itself

Abstract

In many prokaryotes, type III clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated (Cas) systems detect and degrade invasive genetic elements by an RNA-guided, RNA-targeting multisubunit interference complex. The CRISPR-associated protein Csm6 additionally contributes to interference by functioning as a standalone RNase that degrades invader RNA transcripts, but the mechanism linking invader sensing to Csm6 activity is not understood. Here we show that Csm6 proteins are activated through a second messenger generated by the type III interference complex. Upon target RNA binding by the interference complex, its Cas10 subunit converts ATP into a cyclic oligoadenylate product, which allosterically activates Csm6 by binding to its CRISPR-associated Rossmann fold (CARF) domain. CARF domain mutations that abolish allosteric activation inhibit Csm6 activity in vivo, and mutations in the Cas10 Palm domain phenocopy loss of Csm6. Together, these results point to an unprecedented mechanism for regulation of CRISPR interference that bears striking conceptual similarity to oligoadenylate signalling in mammalian innate immunity.

Indexed as

Allosteric RegulationCRISPR-Associated ProteinsCRISPR-Cas SystemsDiffusionEnzyme ActivationEuryarchaeotaImmunity, InnateProtein DomainsRibonucleasesSecond Messenger SystemsThermus thermophilusCRISPR-Associated ProteinsRibonucleases

Identifiers

PMID28722012

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.