Evidence map›Paper›PMID 39457432›Full record

ArticleGenes2024

A Comparative Overview of the Role of Human Ribonucleases in Nonsense-Mediated mRNA Decay.

Paulo J da Costa, Juliane Menezes, Raquel Guedes, Filipa P Reis, Alexandre Teixeira, Margarida Saramago, Sandra C Viegas, Cecília M Arraiano, Luísa Romão

Abstract readComparative Study
In one paragraph

Article in Genes, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Review
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

9 authors.

Paulo J da CostaDepartment of Human Genetics, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal.ORCID 0000-0002-9749-9965
Juliane MenezesDepartment of Human Genetics, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal.ORCID 0000-0003-3727-2096
Raquel GuedesDepartment of Human Genetics, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal.ORCID 0000-0003-4840-7195
Filipa P ReisInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.
Alexandre TeixeiraDepartment of Human Genetics, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal.
Margarida SaramagoInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.ORCID 0000-0003-0458-1036
Sandra C ViegasInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.ORCID 0000-0003-3832-7474
Cecília M ArraianoInstituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.ORCID 0000-0003-1934-9301
Luísa RomãoDepartment of Human Genetics, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal.ORCID 0000-0002-5061-5287

Funding

Fundação para a Ciência e a Tecnologia LA/P/0087/2020Fundação para a Ciência e a Tecnologia SFRH/BD/52495/2014Fundação para a Ciência e a Tecnologia SFRH/BPD/98360/2013Fundação para a Ciência e a Tecnologia UIDB/04046/2020 (DOI: 10.54499/UIDB/04046/2020)Fundação para a Ciência e a Tecnologia UIDB/04612/2020Fundação para a Ciência e a Tecnologia UIDP/04046/2020 (DOI: 10.54499/UIDP/04046/2020)Fundação para a Ciência e a Tecnologia UIDP/04612/2020
6 · The paper itself

Abstract

Eukaryotic cells possess surveillance mechanisms that detect and degrade defective transcripts. Aberrant transcripts include mRNAs with a premature termination codon (PTC), targeted by the nonsense-mediated decay (NMD) pathway, and mRNAs lacking a termination codon, targeted by the nonstop decay (NSD) pathway. The eukaryotic exosome, a ribonucleolytic complex, plays a crucial role in mRNA processing and turnover through its catalytic subunits PM/Scl100 (Rrp6 in yeast), DIS3 (Rrp44 in yeast), and DIS3L1. Additionally, eukaryotic cells have other ribonucleases, such as SMG6 and XRN1, that participate in RNA surveillance. However, the specific pathways through which ribonucleases recognize and degrade mRNAs remain elusive. In this study, we characterized the involvement of human ribonucleases, both nuclear and cytoplasmic, in the mRNA surveillance mechanisms of NMD and NSD. We performed knockdowns of SMG6, PM/Scl100, XRN1, DIS3, and DIS3L1, analyzing the resulting changes in mRNA levels of selected natural NMD targets by RT-qPCR. Additionally, we examined the levels of different human β-globin variants under the same conditions: wild-type, NMD-resistant, NMD-sensitive, and NSD-sensitive. Our results demonstrate that all the studied ribonucleases are involved in the decay of certain endogenous NMD targets. Furthermore, we observed that the ribonucleases SMG6 and DIS3 contribute to the degradation of all β-globin variants, with an exception for βNS in the former case. This is also the case for PM/Scl100, which affects all β-globin variants except the NMD-sensitive variants. In contrast, DIS3L1 and XRN1 show specificity for β-globin WT and NMD-resistant variants. These findings suggest that eukaryotic ribonucleases are target-specific rather than pathway-specific. In addition, our data suggest that ribonucleases play broader roles in mRNA surveillance and degradation mechanisms beyond just NMD and NSD.

Indexed as

ExoribonucleasesExosome Multienzyme Ribonuclease ComplexNonsense Mediated mRNA DecayRNA, MessengerCodon, NonsenseEndoribonucleasesGTP-Binding ProteinsHeLa CellsHumansMicrotubule-Associated ProteinsRibonucleasesRNA StabilityCodon, NonsenseDIS3 protein, humanEndoribonucleasesExoribonucleasesEXOSC10 protein, humanExosome Multienzyme Ribonuclease ComplexGTP-Binding ProteinsHBS1L protein, humanMicrotubule-Associated ProteinsRibonucleasesRNA, MessengerSMG6 protein, humanXRN1 protein, humanmRNA degradationmRNA surveillancenatural NMD targetsnonsense-mediated mRNA decay (NMD)nonstop decay (NSD)quality control

Identifiers

PMID39457432
PMCPMC11507897

What Socratic 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 Socratic graph.