Evidence map›Paper›PMID 25707807›Full record

ArticleNature2015

Cas9 specifies functional viral targets during CRISPR-Cas adaptation.

Robert Heler, Poulami Samai, Joshua W Modell, Catherine Weiner, Gregory W Goldberg, David Bikard, Luciano A Marraffini

Abstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
228citing papers in PubMed, 1 pooled it
22.0field-weighted citation impact, top 1% of its field
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

228 citing papers in PubMed, 1 synthesis or guideline pooled it, 417 citations in OpenAlex.

  1. Pooled it
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  4. Review
  5. Article
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  7. Article
  8. Article
  9. Article
  10. Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026
    Article
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  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Rapid detection ofActa biochimica et biophysica Sinica · 2025
    Article
  18. Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Robert HelerLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Poulami SamaiLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Joshua W ModellLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Catherine WeinerLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Gregory W GoldbergLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
David Bikard1] Laboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA [2] Synthetic Biology Group, Institut Pasteur, 28 Rue du Dr. Roux, 75015 Paris, France.
Luciano A MarraffiniLaboratory of Bacteriology, The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA.
Rockefeller University · USInstitut Pasteur · FR

Funding

Using CRISPR immunity to prevent the spread of virulence traits among pathogensDP2AI104556 · NIAID · ROCKEFELLER UNIVERSITY · PI MARRAFFINI, LUCIANO A · 2012 to 2012
$2.5M
Howard Hughes Medical InstituteNIAID NIH HHS 1DP2AI104556-01NIAID NIH HHS DP2 AI104556
6 · The paper itself

Abstract

Clustered regularly interspaced short palindromic repeat (CRISPR) loci and their associated (Cas) proteins provide adaptive immunity against viral infection in prokaryotes. Upon infection, short phage sequences known as spacers integrate between CRISPR repeats and are transcribed into small RNA molecules that guide the Cas9 nuclease to the viral targets (protospacers). Streptococcus pyogenes Cas9 cleavage of the viral genome requires the presence of a 5'-NGG-3' protospacer adjacent motif (PAM) sequence immediately downstream of the viral target. It is not known whether and how viral sequences flanked by the correct PAM are chosen as new spacers. Here we show that Cas9 selects functional spacers by recognizing their PAM during spacer acquisition. The replacement of cas9 with alleles that lack the PAM recognition motif or recognize an NGGNG PAM eliminated or changed PAM specificity during spacer acquisition, respectively. Cas9 associates with other proteins of the acquisition machinery (Cas1, Cas2 and Csn2), presumably to provide PAM-specificity to this process. These results establish a new function for Cas9 in the genesis of prokaryotic immunological memory.

Indexed as

CRISPR-Cas SystemsBase SequenceClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsDNA, ViralMolecular Sequence DataNucleotide MotifsProtein BindingProtein Structure, TertiaryStaphylococcus aureusStreptococcus pyogenesSubstrate SpecificityCRISPR-Associated ProteinsDNA, Viral

Identifiers

PMID25707807
PMCPMC4385744
OpenAlexW2060259395

What OpenQuestion holds

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LicenceTDM
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.