Evidence map›Paper›PMID 29954833›Full record

ArticleGenes & development2018

Yra1-bound RNA-DNA hybrids cause orientation-independent transcription-replication collisions and telomere instability.

María García-Rubio, Paula Aguilera, Juan Lafuente-Barquero, José F Ruiz, Marie-Noelle Simon, Vincent Geli, Ana G Rondón, Andrés Aguilera

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing 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

49 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. ATR activity controls stem cell quiescence via the cyclin F-SCF complex.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

8 authors at 2 institutions in 2 countries.

María García-Rubio *Andalusian Center of Molecular Biology and Regenerative Medicine (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Pablo de Olavide, 41092 Seville, Spain.
Paula Aguilera *Marseille Cancer Research Center (CRCM), U1068, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR7258, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, Institut Paoli-Calmettes, Equipe Labellisée Ligue, 13273 Marseille, France.
Juan Lafuente-BarqueroAndalusian Center of Molecular Biology and Regenerative Medicine (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Pablo de Olavide, 41092 Seville, Spain.
José F RuizAndalusian Center of Molecular Biology and Regenerative Medicine (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Pablo de Olavide, 41092 Seville, Spain.
Marie-Noelle SimonMarseille Cancer Research Center (CRCM), U1068, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR7258, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, Institut Paoli-Calmettes, Equipe Labellisée Ligue, 13273 Marseille, France.
Vincent GeliMarseille Cancer Research Center (CRCM), U1068, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR7258, Centre National de la Recherche Scientifique (CNRS), Aix Marseille University, Institut Paoli-Calmettes, Equipe Labellisée Ligue, 13273 Marseille, France.
Ana G RondónAndalusian Center of Molecular Biology and Regenerative Medicine (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Pablo de Olavide, 41092 Seville, Spain.
Andrés AguileraAndalusian Center of Molecular Biology and Regenerative Medicine (CABIMER), Universidad de Sevilla-Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Pablo de Olavide, 41092 Seville, Spain.ORCID 0000-0003-4782-1714
Consejo Superior de Investigaciones Científicas · ESCentre National de la Recherche Scientifique · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

R loops are an important source of genome instability, largely due to their negative impact on replication progression. Yra1/ALY is an abundant RNA-binding factor conserved from yeast to humans and required for mRNA export, but its excess causes lethality and genome instability. Here, we show that, in addition to ssDNA and ssRNA, Yra1 binds RNA-DNA hybrids in vitro and, when artificially overexpressed, can be recruited to chromatin in an RNA-DNA hybrid-dependent manner, stabilizing R loops and converting them into replication obstacles in vivo. Importantly, an excess of Yra1 increases R-loop-mediated genome instability caused by transcription-replication collisions regardless of whether they are codirectional or head-on. It also induces telomere shortening in telomerase-negative cells and accelerates senescence, consistent with a defect in telomere replication. Our results indicate that RNA-DNA hybrids form transiently in cells regardless of replication and, after stabilization by excess Yra1, compromise genome integrity, in agreement with a two-step model of R-loop-mediated genome instability. This work opens new perspectives to understand transcription-associated genome instability in repair-deficient cells, including tumoral cells.

Indexed as

DNA ReplicationTranscription, GeneticChromatinChromosomal InstabilityNuclear ProteinsNucleic Acid HybridizationProtein BindingRNA-Binding ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTelomereChromatinNuclear ProteinsRNA-Binding ProteinsSaccharomyces cerevisiae ProteinsYRA1 protein, S cerevisiaeR looptelomerestranscription–replication collisionYra1

Identifiers

PMID29954833
PMCPMC6075034
OpenAlexW2810632592

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.