Evidence map›Paper›PMID 34168151›Full record

ArticleNature communications2021

The human nucleoporin Tpr protects cells from RNA-mediated replication stress.

Martin Kosar, Michele Giannattasio, Daniele Piccini, Apolinar Maya-Mendoza, Francisco García-Benítez, Jirina Bartkova, Sonia I Barroso, Hélène Gaillard, Emanuele Martini, Umberto Restuccia and 12 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.1field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
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  8. Lamin A/C loss promotes R-loop-mediated genomic instability and poor survival in small-cell lung cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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  13. Advances in the understanding of nuclear pore complexes in human diseases.Journal of cancer research and clinical oncology · 2024
    Review
  14. Review
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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

22 authors at 9 institutions in 7 countries.

Martin KosarIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.ORCID 0000-0002-9400-2327
Michele GiannattasioIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.ORCID 0000-0001-7099-5718
Daniele PicciniIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.ORCID 0000-0001-9200-8496
Apolinar Maya-MendozaDanish Cancer Society Research Center, Copenhagen, Denmark.ORCID 0000-0001-7452-9896
Francisco García-BenítezCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, Seville, Spain.
Jirina BartkovaDanish Cancer Society Research Center, Copenhagen, Denmark.
Sonia I BarrosoCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, Seville, Spain.ORCID 0000-0002-0062-2016
Hélène GaillardCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, Seville, Spain.ORCID 0000-0002-5740-0641
Emanuele MartiniIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.ORCID 0000-0002-3375-7726
Umberto RestucciaIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.
Miguel Angel Ramirez-OteroIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.ORCID 0000-0001-8428-1150
Massimiliano GarreIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.
Eleonora VergaIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.
Miguel Andújar-SánchezPathology Department, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, Spain.ORCID 0000-0002-4858-6915
Scott MaynardDanish Cancer Society Research Center, Copenhagen, Denmark.ORCID 0000-0001-5625-936X
Zdenek HodnyInstitute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Vincenzo CostanzoIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.
Amit KumarGenome & Cell Integrity Laboratory, CSIR-Indian Institute of Toxicology Research, Lucknow, India.ORCID 0000-0003-1732-440X
Angela BachiIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy.ORCID 0000-0003-4842-6556
Andrés AguileraCentro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla-CSIC, Seville, Spain. aguilo@us.es.ORCID 0000-0003-4782-1714
Jiri BartekInstitute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic. jb@cancer.dk.ORCID 0000-0003-2013-7525
Marco FoianiIFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milano, Italy. marco.foiani@ifom.eu.ORCID 0000-0003-4795-834X
IFOM · ITCentro Andaluz de Biología Molecular y Medicina Regenerativa · ESUniversity of Milan · ITDanish Cancer Society · DKScience for Life Laboratory · SECzech Academy of Sciences · CZCzech Academy of Sciences, Institute of Molecular Genetics · CZHospital Universitario Insular de Gran Canaria · ESIndian Institute of Toxicology Research · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although human nucleoporin Tpr is frequently deregulated in cancer, its roles are poorly understood. Here we show that Tpr depletion generates transcription-dependent replication stress, DNA breaks, and genomic instability. DNA fiber assays and electron microscopy visualization of replication intermediates show that Tpr deficient cells exhibit slow and asymmetric replication forks under replication stress. Tpr deficiency evokes enhanced levels of DNA-RNA hybrids. Additionally, complementary proteomic strategies identify a network of Tpr-interacting proteins mediating RNA processing, such as MATR3 and SUGP2, and functional experiments confirm that their depletion trigger cellular phenotypes shared with Tpr deficiency. Mechanistic studies reveal the interplay of Tpr with GANP, a component of the TREX-2 complex. The Tpr-GANP interaction is supported by their shared protein level alterations in a cohort of ovarian carcinomas. Our results reveal links between nucleoporins, DNA transcription and replication, and the existence of a network physically connecting replication forks with transcription, splicing, and mRNA export machinery.

Indexed as

DNA ReplicationAcetyltransferasesCell SurvivalDNA DamageGenomic InstabilityHeLa CellsHumansIntracellular Signaling Peptides and ProteinsNeoplasmsNuclear Pore Complex ProteinsProtein Interaction MapsProto-Oncogene ProteinsRNA TransportAcetyltransferasesIntracellular Signaling Peptides and ProteinsMCM3AP protein, humanNuclear Pore Complex ProteinsProto-Oncogene ProteinsTPR protein, human

Identifiers

PMID34168151
PMCPMC8225803
OpenAlexW3177138901

What OpenQuestion holds

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LicenceCC BY
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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.