Evidence map›Paper›PMID 41577687›Full record

ArticleNature communications2026

CRISPR-Cas9 trans-cleavage is hindered by a flanked R-loop, an elongated spacer, and an inactive HNH domain.

Roser Montagud-Martínez, Raúl Ruiz, Sara Baldanta, Rubén Delicado-Mateo, Guillermo Rodrigo

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

5 authors.

Roser Montagud-MartínezInstitute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, Paterna, Spain.ORCID 0000-0003-4487-1599
Raúl RuizInstitute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, Paterna, Spain.ORCID 0000-0002-5300-2240
Sara BaldantaInstitute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, Paterna, Spain.ORCID 0000-0002-4558-9774
Rubén Delicado-MateoInstitute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, Paterna, Spain.ORCID 0009-0002-7007-7401
Guillermo RodrigoInstitute for Integrative Systems Biology (I2SysBio), CSIC - University of Valencia, Paterna, Spain. guillermo.rodrigo@csic.es.ORCID 0000-0002-1871-9617

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cas9 can process poly(T) single-stranded DNA molecules upon activation in an RNA-guided manner. Here, we uncover key determinants underlying this function. First, we show that unflanked R-loops in the RNA 5' side favor trans-cleavage activity, which occur when targeting short double-stranded DNA molecules. Second, we show that elongated guide RNA spacers beyond the canonical 20 bases, even by a few bases, severely impair this collateral activity. Third, although trans-cleavage is mediated by the RuvC domain, we show that a catalytically active HNH domain contributes to an efficient process. Analysis of structural models provides tentative mechanistic insights. Together, these findings illustrate that fine modulation of Cas9 function can be achieved.

Indexed as

CRISPR-Cas SystemsR-Loop StructuresRNA, Guide, CRISPR-Cas SystemsDNAModels, MolecularProtein DomainsDNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID41577687
PMCPMC12936194

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.