Evidence map›Paper›PMID 26896796›Full record

ArticleMolecular & cellular proteomics : MCP2016

Proteomic Analysis Reveals Branch-specific Regulation of the Unfolded Protein Response by Nonsense-mediated mRNA Decay.

Jana Sieber, Christian Hauer, Madhuri Bhuvanagiri, Stefan Leicht, Jeroen Krijgsveld, Gabriele Neu-Yilik, Matthias W Hentze, Andreas E Kulozik

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.1field-weighted citation impact, top 15% 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

23 citing papers in PubMed, 32 citations in OpenAlex.

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  18. RNA Decay Factor UPF1 Promotes Protein Decay: A Hidden Talent.BioEssays : news and reviews in molecular, cellular and developmental biology · 2018
    Review
  19. Stress and the nonsense-mediated RNA decay pathway.Cellular and molecular life sciences : CMLS · 2017
    Review
  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 1 country.

Jana SieberFrom the ‡Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, University of Heidelberg, Heidelberg, Germany; §Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany;
Christian HauerFrom the ‡Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, University of Heidelberg, Heidelberg, Germany; §Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany; ¶European Molecular Biology Laboratory, Heidelberg, Germany.
Madhuri BhuvanagiriFrom the ‡Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, University of Heidelberg, Heidelberg, Germany; §Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany;
Stefan Leicht¶European Molecular Biology Laboratory, Heidelberg, Germany.
Jeroen Krijgsveld¶European Molecular Biology Laboratory, Heidelberg, Germany.
Gabriele Neu-YilikFrom the ‡Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, University of Heidelberg, Heidelberg, Germany; §Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany;
Matthias W HentzeFrom the ‡Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, University of Heidelberg, Heidelberg, Germany; ¶European Molecular Biology Laboratory, Heidelberg, Germany.ORCID 0000-0002-4023-7876
Andreas E KulozikFrom the ‡Molecular Medicine Partnership Unit, European Molecular Biology Laboratory, University of Heidelberg, Heidelberg, Germany; §Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany; andreas.kulozik@med.uni-heidelberg.de.
European Molecular Biology Laboratory · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nonsense-mediated mRNA decay (NMD) has originally been described as a surveillance mechanism to inhibit the expression of mRNAs with truncated open reading frames (ORFs) and to contribute to the fidelity of gene expression. It is now recognized that NMD also controls the expression of physiological genes with "intact" mRNA. Stress can decrease NMD efficiency and thus increase the mRNA levels of physiological NMD targets. As stress can also inhibit translation, the net outcome for shaping the proteome is difficult to predict. We have thus analyzed de novo protein synthesis in response to NMD inhibition or the induction of mild endoplasmic reticulum (ER) stress by treatment of cells with the reducing agent dithiotreitol (DTT). For this purpose, we combined pulsed azidohomoalanine (AHA) and stable isotope labeling by amino acids in cell culture (SILAC). Labeled proteins were purified by click chemistry-based covalent coupling to agarose beads, trypsinized, fractionated, and analyzed by mass spectrometry (MS). We find that mild ER stress up-regulates the de novo synthesis of components of all three branches of the unfolded protein response (PERK, IRE1 and ATF6) without increasing eIF2α phosphorylation or impairing of protein translation. In contrast, inhibition of NMD induces de novo protein synthesis of downstream targets of the PERK and IRE1 pathways, whereas we could not detect regulation of ATF6-responsive genes. These data thus support a model that implicates a positive feedback loop of ER stress inhibiting NMD efficiency which further promotes the ER stress response in a branch-specific manner.

Indexed as

AlanineDithiothreitolEndoplasmic Reticulum StressGene Regulatory NetworksHeLa CellsHumansIsotope LabelingLiquid-Liquid ExtractionNonsense Mediated mRNA DecayProteomicsTandem Mass SpectrometryUnfolded Protein ResponseAlanineazidohomoalanineDithiothreitol

Identifiers

PMID26896796
PMCPMC4858941
OpenAlexW2276971537

What OpenQuestion holds

Textmetadata
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.