Evidence map›Paper›PMID 26593719›Full record

ArticleMolecular cell2015

Discovery and Functional Characterization of Diverse Class 2 CRISPR-Cas Systems.

Sergey Shmakov, Omar O Abudayyeh, Kira S Makarova, Yuri I Wolf, Jonathan S Gootenberg, Ekaterina Semenova, Leonid Minakhin, Julia Joung, Silvana Konermann, Konstantin Severinov and 2 more

Abstract read
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 626 papers.

0numbers the graph read from it
0cells of the map it votes in
626citing 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

626 citing papers in PubMed.

  1. CRISPR/Cas Systems: Biological Basis and Genome Editing Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Role of Chromatin-Associated RNAs in Eye Physiology and Pathology.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. CRISPR/Cas13a: Compensatory Target Activation Mechanism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

566 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

12 authors.

Sergey ShmakovSkolkovo Institute of Science and Technology, Skolkovo, 143025, Russia; NCBI, NLM, NIH, Bethesda, MD 20894, USA.
Omar O AbudayyehBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kira S MakarovaNCBI, NLM, NIH, Bethesda, MD 20894, USA.
Yuri I WolfNCBI, NLM, NIH, Bethesda, MD 20894, USA.
Jonathan S GootenbergBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ekaterina SemenovaWaksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Leonid MinakhinWaksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Julia JoungBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Silvana KonermannBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Konstantin SeverinovSkolkovo Institute of Science and Technology, Skolkovo, 143025, Russia; Waksman Institute for Microbiology, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182, Russia.
Feng ZhangBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: zhang@broadinstitute.org.
Eugene V KooninNCBI, NLM, NIH, Bethesda, MD 20894, USA. Electronic address: koonin@ncbi.nlm.nih.gov.

Funding

Comparative Analysis Of Completely Sequenced GenomesZIALM000073 · NLM · NATIONAL LIBRARY OF MEDICINE · PI KOONIN, EUGENE V · 2009 to 2025
$43.1M
Isogenic Human Pluripotent Stem Cell-Based Models of Human Disease MutationsR01DK097768 · NIDDK · BROAD INSTITUTE, INC. · PI COWAN, CHAD ALBERT, ZHANG, FENG · 2012 to 2016
$11.0M
Finding Protein Sequence Motifs--Methods And ApplicationsZIALM000061 · NLM · NATIONAL LIBRARY OF MEDICINE · PI KOONIN, EUGENE V · 2009 to 2025
$10.6M
Massively-parallel functional interrogation of psychiatric geneticsR01MH110049 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2015 to 2019
$5.5M
Probing Neuropsychiatric Diseases Using Targeted Epigenome and Genome EngineeringDP1MH100706 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2012 to 2016
$4.3M
The Function of Small RNA-Based viral Defense System in E. coli - Renewal 1R01GM104071 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI SEMENOVA, EKATERINA · 2013 to 2024
$3.9M
NCCDPHP CDC HHS 5DP1-MH100706NIDDK NIH HHS 5R01DK097768-03NIDDK NIH HHS R01 DK097768NIGMS NIH HHS GM10407NIGMS NIH HHS R01 GM104071NIMH NIH HHS DP1 MH100706NIMH NIH HHS R01 MH110049
6 · The paper itself

Abstract

Microbial CRISPR-Cas systems are divided into Class 1, with multisubunit effector complexes, and Class 2, with single protein effectors. Currently, only two Class 2 effectors, Cas9 and Cpf1, are known. We describe here three distinct Class 2 CRISPR-Cas systems. The effectors of two of the identified systems, C2c1 and C2c3, contain RuvC-like endonuclease domains distantly related to Cpf1. The third system, C2c2, contains an effector with two predicted HEPN RNase domains. Whereas production of mature CRISPR RNA (crRNA) by C2c1 depends on tracrRNA, C2c2 crRNA maturation is tracrRNA independent. We found that C2c1 systems can mediate DNA interference in a 5'-PAM-dependent fashion analogous to Cpf1. However, unlike Cpf1, which is a single-RNA-guided nuclease, C2c1 depends on both crRNA and tracrRNA for DNA cleavage. Finally, comparative analysis indicates that Class 2 CRISPR-Cas systems evolved on multiple occasions through recombination of Class 1 adaptation modules with effector proteins acquired from distinct mobile elements.

Indexed as

BacteriaBacterial ProteinsEvolution, MolecularRibonucleasesRNA, BacterialCRISPR-Cas SystemsProtein Structure, TertiaryRecombination, GeneticBacterial ProteinsRibonucleasesRNA, BacterialCas9computational discovery pipelineCpf1CRISPR-Cas adaptive immunitycrRNAHEPN domainPAMRNA-seqRuvC-like endonucleasetracrRNA

Identifiers

PMID26593719
PMCPMC4660269

What OpenQuestion holds

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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.