Evidence map›Paper›PMID 30344094›Full record

ArticleMolecular cell2018

A Reverse Transcriptase-Cas1 Fusion Protein Contains a Cas6 Domain Required for Both CRISPR RNA Biogenesis and RNA Spacer Acquisition.

Georg Mohr, Sukrit Silas, Jennifer L Stamos, Kira S Makarova, Laura M Markham, Jun Yao, Patricia Lucas-Elío, Antonio Sanchez-Amat, Andrew Z Fire, Eugene V Koonin and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

17 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
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

11 authors at 4 institutions in 2 countries.

Georg MohrInstitute for Cellular and Molecular Biology and Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
Sukrit SilasDepartment of Pathology, Stanford University, Stanford, CA 94305, USA; Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA.
Jennifer L StamosInstitute for Cellular and Molecular Biology and Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
Kira S MakarovaNational Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA.
Laura M MarkhamInstitute for Cellular and Molecular Biology and Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
Jun YaoInstitute for Cellular and Molecular Biology and Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA.
Patricia Lucas-ElíoDepartment of Genetics and Microbiology, Universidad de Murcia, Murcia 30100, Spain.
Antonio Sanchez-AmatDepartment of Genetics and Microbiology, Universidad de Murcia, Murcia 30100, Spain.
Andrew Z FireDepartment of Pathology, Stanford University, Stanford, CA 94305, USA.
Eugene V KooninNational Center for Biotechnology Information, National Library of Medicine, NIH, Bethesda, MD 20894, USA.
Alan M LambowitzInstitute for Cellular and Molecular Biology and Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, USA. Electronic address: lambowitz@austin.utexas.edu.
The University of Texas at Austin · USNational Center for Biotechnology Information · USStanford University · USUniversidad de Murcia · ES

Funding

Comparative Analysis Of Completely Sequenced GenomesZIALM000073 · NLM · NATIONAL LIBRARY OF MEDICINE · PI KOONIN, EUGENE V · 2009 to 2025
$43.1M
GENE REGULATION DURING EARLY DEVELOPMENT OF C. ELEGANSR01GM037706 · NIGMS · STANFORD UNIVERSITY · PI FIRE, ANDREW Z. · 1987 to 2018
$11.0M
RETROPLASMID AND GROUP II INTRON REVERSE TRANSCRIPTASESR01GM037949 · NIGMS · UNIVERSITY OF TEXAS AUSTIN · PI LAMBOWITZ, ALAN M. · 1986 to 2019
$8.6M
Howard Hughes Medical InstituteIntramural NIH HHS ZIA LM000073NIGMS NIH HHS R01 GM037706NIGMS NIH HHS R01 GM037949
6 · The paper itself

Abstract

Prokaryotic CRISPR-Cas systems provide adaptive immunity by integrating portions of foreign nucleic acids (spacers) into genomic CRISPR arrays. Cas6 proteins then process CRISPR array transcripts into spacer-derived RNAs (CRISPR RNAs; crRNAs) that target Cas nucleases to matching invaders. We find that a Marinomonas mediterranea fusion protein combines three enzymatic domains (Cas6, reverse transcriptase [RT], and Cas1), which function in both crRNA biogenesis and spacer acquisition from RNA and DNA. We report a crystal structure of this divergent Cas6, identify amino acids required for Cas6 activity, show that the Cas6 domain is required for RT activity and RNA spacer acquisition, and demonstrate that CRISPR-repeat binding to Cas6 regulates RT activity. Co-evolution of putative interacting surfaces suggests a specific structural interaction between the Cas6 and RT domains, and phylogenetic analysis reveals repeated, stable association of free-standing Cas6s with CRISPR RTs in multiple microbial lineages, indicating that a functional interaction between these proteins preceded evolution of the fusion.

Indexed as

Base SequenceClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCRISPR-Cas SystemsDNAEndonucleasesMarinomonasPhylogenyRNARNA-Directed DNA PolymeraseSubstrate SpecificityCRISPR-Associated ProteinsDNAEndonucleasesRNARNA-Directed DNA Polymeraseadaptive immunityCas1CRISPR adaptationCRISPR-CascrRNA processingcrystal structureevolutionfusion proteinreverse transcriptase

Identifiers

PMID30344094
PMCPMC6242336
OpenAlexW2896308771

What OpenQuestion holds

Textmetadata
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.