Evidence map›Paper›PMID 28306505›Full record

ArticleMolecular cell2017

Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation.

Olga Sin, Tristan de Jong, Alejandro Mata-Cabana, Michelle Kudron, Mohamad Amr Zaini, Francesco A Aprile, Renée I Seinstra, Esther Stroo, Roméo Willinge Prins, Céline N Martineau and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

9 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. RNA Polymerase III, Ageing and Longevity.Frontiers in genetics · 2021
    Review
  6. Regulation of Age-Related Protein Toxicity.Frontiers in cell and developmental biology · 2021
    Review
  7. Review
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 5 institutions in 5 countries.

Olga SinEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands; Graduate Program in Areas of Basic and Applied Biology, Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal.
Tristan de JongEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Alejandro Mata-CabanaEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Michelle KudronDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Mohamad Amr ZainiEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Francesco A AprileDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Renée I SeinstraEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Esther StrooEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Roméo Willinge PrinsEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Céline N MartineauEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Hai Hui WangEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Wytse HogewerfEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Anne SteinhofMax Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
Erich E WankerMax Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
Michele VendruscoloDepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Cornelis F CalkhovenEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands.
Valerie ReinkeDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Victor GuryevEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands. Electronic address: v.guryev@umcg.nl.
Ellen A A NollenEuropean Research Institute for the Biology of Ageing, University of Groningen, University Medical Centre Groningen, 9700 AD Groningen, the Netherlands. Electronic address: e.a.a.nollen@umcg.nl.
University of Groningen · NLMax Delbrück Center · DEUniversity of Cambridge · GBYale University · USUniversidade do Porto · PT

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Resource ProjectU41HG007355 · NHGRI · UNIVERSITY OF WASHINGTON · PI WATERSTON, ROBERT H · 2013 to 2021
$20.8M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM007499 · NIGMS · YALE UNIVERSITY · PI CARLSON, JOHN R, REINKE, VALERIE J · 1985 to 2022
$13.9M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
NCATS NIH HHS UL1 TR001863NHGRI NIH HHS U41 HG007355NIGMS NIH HHS T32 GM007499NIH HHS P40 OD010440
6 · The paper itself

Abstract

Protein aggregation is associated with age-related neurodegenerative disorders, such as Alzheimer's and polyglutamine diseases. As a causal relationship between protein aggregation and neurodegeneration remains elusive, understanding the cellular mechanisms regulating protein aggregation will help develop future treatments. To identify such mechanisms, we conducted a forward genetic screen in a C. elegans model of polyglutamine aggregation and identified the protein MOAG-2/LIR-3 as a driver of protein aggregation. In the absence of polyglutamine, MOAG-2/LIR-3 regulates the RNA polymerase III-associated transcription of small non-coding RNAs. This regulation is lost in the presence of polyglutamine, which mislocalizes MOAG-2/LIR-3 from the nucleus to the cytosol. We then show biochemically that MOAG-2/LIR-3 can also catalyze the aggregation of polyglutamine-expanded huntingtin. These results suggest that polyglutamine can induce an aggregation-promoting activity of MOAG-2/LIR-3 in the cytosol. The concept that certain aggregation-prone proteins can convert other endogenous proteins into drivers of aggregation and toxicity adds to the understanding of how cellular homeostasis can be deteriorated in protein misfolding diseases.

Indexed as

Protein AggregatesProtein Aggregation, PathologicalActive Transport, Cell NucleusAnimalsAnimals, Genetically ModifiedBinding SitesCaenorhabditis elegansCaenorhabditis elegans ProteinsCell NucleusCytosolDisease Models, AnimalNeurodegenerative DiseasesPeptidesPromoter Regions, GeneticProtein BindingRNA InterferenceCaenorhabditis elegans ProteinsLIR-3 protein, C elegansPeptidespolyglutamineProtein AggregatesRNA Polymerase IIIRNA, Small UntranslatedTranscription FactorsC. elegansMOAG-2/LIR-3non-coding RNApolyglutamineprotein aggregationprotein homeostasisprotein quality controlRNA polymerase IIIsnoRNAtRNA

Identifiers

PMID28306505
PMCPMC5364375
OpenAlexW2594944156

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.