Evidence map›Paper›PMID 27096362›Full record

ArticleNature2016

The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA.

Ines Fonfara, Hagen Richter, Majda Bratovič, Anaïs Le Rhun, Emmanuelle Charpentier

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 491 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
491citing papers in PubMed, 1 pooled it
55.0field-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

491 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,012 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Molecular mechanisms and biotechnology applications of CRISPR-Cas12a.Nature reviews. Molecular cell biology · 2026
    Review
  10. Article
  11. Article
  12. Machine Learning for CRISPR-Based Diagnostics.International journal of molecular sciences · 2026
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. CRISPR Interference to Inhibit Oncogenes for Cancer Therapy.International journal of molecular sciences · 2026
    Review
  18. Article
  19. Review
  20. Article

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

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

5 authors at 2 institutions in 2 countries.

Ines FonfaraThe Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University, Umeå 90187, Sweden.
Hagen RichterHelmholtz Centre for Infection Research, Department of Regulation in Infection Biology, Braunschweig 38124, Germany.
Majda BratovičHelmholtz Centre for Infection Research, Department of Regulation in Infection Biology, Braunschweig 38124, Germany.
Anaïs Le RhunThe Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University, Umeå 90187, Sweden.
Emmanuelle CharpentierThe Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå Centre for Microbial Research (UCMR), Department of Molecular Biology, Umeå University, Umeå 90187, Sweden.
Helmholtz Centre for Infection Research · DEUmeå University · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR-Cas systems that provide defence against mobile genetic elements in bacteria and archaea have evolved a variety of mechanisms to target and cleave RNA or DNA. The well-studied types I, II and III utilize a set of distinct CRISPR-associated (Cas) proteins for production of mature CRISPR RNAs (crRNAs) and interference with invading nucleic acids. In types I and III, Cas6 or Cas5d cleaves precursor crRNA (pre-crRNA) and the mature crRNAs then guide a complex of Cas proteins (Cascade-Cas3, type I; Csm or Cmr, type III) to target and cleave invading DNA or RNA. In type II systems, RNase III cleaves pre-crRNA base-paired with trans-activating crRNA (tracrRNA) in the presence of Cas9 (refs 13, 14). The mature tracrRNA-crRNA duplex then guides Cas9 to cleave target DNA. Here, we demonstrate a novel mechanism in CRISPR-Cas immunity. We show that type V-A Cpf1 from Francisella novicida is a dual-nuclease that is specific to crRNA biogenesis and target DNA interference. Cpf1 cleaves pre-crRNA upstream of a hairpin structure formed within the CRISPR repeats and thereby generates intermediate crRNAs that are processed further, leading to mature crRNAs. After recognition of a 5'-YTN-3' protospacer adjacent motif on the non-target DNA strand and subsequent probing for an eight-nucleotide seed sequence, Cpf1, guided by the single mature repeat-spacer crRNA, introduces double-stranded breaks in the target DNA to generate a 5' overhang. The RNase and DNase activities of Cpf1 require sequence- and structure-specific binding to the hairpin of crRNA repeats. Cpf1 uses distinct active domains for both nuclease reactions and cleaves nucleic acids in the presence of magnesium or calcium. This study uncovers a new family of enzymes with specific dual endoribonuclease and endonuclease activities, and demonstrates that type V-A constitutes the most minimalistic of the CRISPR-Cas systems so far described.

Indexed as

DNA CleavageRNA Processing, Post-TranscriptionalBacterial ProteinsBase SequenceCalciumCatalytic DomainClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCRISPR-Cas SystemsFrancisellaMolecular Sequence DataNucleic Acid ConformationRNA, BacterialRNA, Guide, CRISPR-Cas SystemsRNA PrecursorsSubstrate SpecificityBacterial ProteinsCalciumCRISPR-Associated ProteinsRNA, BacterialRNA, Guide, CRISPR-Cas SystemsRNA Precursors

Identifiers

PMID27096362
OpenAlexW2341405505

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.