Evidence map›Paper›PMID 42556347›Full record

ArticleMolecular cell2026

Stepwise DNA-unwinding gates TnpB genome-editing activity.

Zehan Zhou, Iren Saffarian-Deemyad, Honglue Shi, Trevor Weiss, Muhammad Moez Ur-Rehman, Kamakshi Vohra, Petr Skopintsev, Peter H Yoon, Marena I Trinidad, Conner J Langeberg and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Virus-induced transgene- and tissue culture-free heritable genome editing in tomato.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors.

Zehan ZhouInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Iren Saffarian-DeemyadDepartment of Physics, Stanford University, Stanford, CA 94305, USA.
Honglue ShiInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Trevor WeissDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Muhammad Moez Ur-RehmanInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Kamakshi VohraInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Petr SkopintsevInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Peter H YoonInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Marena I TrinidadInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; University of California, Berkeley, University of California, San Francisco Graduate Program in Bioengineering, Berkeley, CA 94720, USA.
Conner J LangebergInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Maris KamaluDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jasmine AmerasekeraDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yuxing ZhouDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Erin E DohertyInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Kevin D P ArisDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Biophysics Program, Stanford University, Stanford, CA 94305, USA.
Noor Al-SayyadDepartment of Physics, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Brittney W ThorntonInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Rachel F WeissmanInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Kevin M WaskoInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Isabel Esain-GarciaInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA.
Evan C DeTurkInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
David F SavageInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Steven E JacobsenDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: jacobsen@ucla.edu.
Zev BryantDepartment of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University Medical Center, Stanford, CA 94305, USA. Electronic address: zevry@stanford.edu.
Jennifer A DoudnaInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA; Li Ka Shing Center for Genomic Engineering, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Gladstone Institute of Data Science and Biotechnology, San Francisco, CA 94158, USA; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA 94158, USA. Electronic address: doudna@berkeley.edu.

Funding

Structural Dynamics and Mechanochemical Coupling in Nucleoprotein MachinesR01GM106159 · NIGMS · STANFORD UNIVERSITY · PI Zev Bryant · 2014 to 2026
$3.2M
The dynamics, functions and evolution of a miniature RNA-guided enzymeK99GM160778 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Honglue Shi · 2025 to 2026
$240k
Precision Deaminases to Expand the Scope of Diseases Amenable to CRISPR-mediated CorrectionF32GM153031 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Erin E Doherty · 2024 to 2026
$229k
NIGMS NIH HHS F32 GM153031NIGMS NIH HHS K99 GM160778NIGMS NIH HHS R01 GM106159
6 · The paper itself

Abstract

TnpB is a compact RNA-guided endonuclease and an evolutionary ancestor of CRISPR-Cas12 that offers a promising platform for genome engineering. However, the genome-editing activity of TnpBs remains limited, and its underlying determinants are poorly understood. Here, we used biochemical and single-molecule assays to examine the DNA-unwinding mechanism of Youngiibacter multivorans TnpB (Ymu1 TnpB). DNA unwinding proceeds through a discrete, long-lived, partially unwound intermediate state before reaching a fully unwound open state. The open state forms inefficiently and collapses readily in the absence of negative supercoiling. An optimized variant, H4W-L304F-V305R (Ymu1-WFR), stabilizes formation of both the intermediate and open states, resulting in enhanced DNA cleavage in vitro and increased genome editing in plants. These findings identify the physical basis for the observed minimal activities of natural TnpBs, revealing how stabilizing specific unwinding states enables efficient DNA targeting.

Indexed as

Bacterial ProteinsEndonucleasesGene EditingCRISPR-Cas SystemsNucleic Acid ConformationBacterial ProteinsEndonucleasesCRISPR-CasDNA unwindingenergy landscapegenome editingplant genome editingprotein engineeringR-loop formationRNA-guided nucleasesingle-molecule biophysicsTnpB

Identifiers

PMID42556347
PMCPMC13577324

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.