Evidence map›Paper›PMID 34088960›Full record

ArticleScientific reports2021

ALS-linked FUS mutants affect the localization of U7 snRNP and replication-dependent histone gene expression in human cells.

Ankur Gadgil, Agnieszka Walczak, Agata Stępień, Jonas Mechtersheimer, Agnes Lumi Nishimura, Christopher E Shaw, Marc-David Ruepp, Katarzyna Dorota Raczyńska

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 24% 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

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. The Novel Role of hnRNP UL1 in Human Cell Nucleoli.International journal of biological sciences · 2022
    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 3 institutions in 3 countries.

Ankur GadgilDepartment of Gene Expression, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.ORCID 0000-0001-5155-4079
Agnieszka WalczakDepartment of Gene Expression, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.
Agata StępieńDepartment of Gene Expression, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland.
Jonas MechtersheimerUK Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Strand, London, WC2R 2LS, UK.
Agnes Lumi NishimuraUK Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Strand, London, WC2R 2LS, UK.
Christopher E ShawUK Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Strand, London, WC2R 2LS, UK.
Marc-David RueppUK Dementia Research Institute Centre at King's College London, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Strand, London, WC2R 2LS, UK.ORCID 0000-0003-3264-9800
Katarzyna Dorota RaczyńskaDepartment of Gene Expression, Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University, Poznan, Poland. doracz@amu.edu.pl.ORCID 0000-0002-3712-3528
Adam Mickiewicz University in Poznań · PLKing's College London · GBUniversity of Auckland · NZ

Funding

Medical Research Council G0500289Medical Research Council G0900635Medical Research Council G0900688Medical Research Council G1100695Medical Research Council MC_G1000733Medical Research Council MC_PC_17115Medical Research Council MR/L021803/1Motor Neurone Disease Association SHAW/APR15/970-797Motor Neurone Disease Association SHAW/NOV14/985-797
6 · The paper itself

Abstract

Genes encoding replication-dependent histones lack introns, and the mRNAs produced are a unique class of RNA polymerase II transcripts in eukaryotic cells that do not end in a polyadenylated tail. Mature mRNAs are thus formed by a single endonucleolytic cleavage that releases the pre-mRNA from the DNA and is the only processing event necessary. U7 snRNP is one of the key factors that determines the cleavage site within the 3'UTR of replication-dependent histone pre-mRNAs. We have previously showed that the FUS protein interacts with U7 snRNA/snRNP and regulates the expression of histone genes by stimulating transcription and 3' end maturation. Mutations in the FUS gene first identified in patients with amyotrophic lateral sclerosis (ALS) lead to the accumulation of the FUS protein in cytoplasmic inclusions. Here, we report that mutations in FUS lead to disruption of the transcriptional activity of FUS and mislocalization of U7 snRNA/snRNP in cytoplasmic aggregates in cellular models and primary neurons. As a consequence, decreased transcriptional efficiency and aberrant 3' end processing of histone pre-mRNAs were observed. This study highlights for the first time the deregulation of replication-dependent histone gene expression and its involvement in ALS.

Indexed as

Gene Expression RegulationMutation3' Untranslated RegionsAmyotrophic Lateral SclerosisCell Line, TumorCell NucleusCytoplasmGene Expression ProfilingHeLa CellsHistonesHumansIn Situ Hybridization, FluorescenceNeurosciencesPlasmidsRibonucleoproteins, Small NuclearRibonucleoprotein, U7 Small Nuclear3' Untranslated RegionsFUS protein, humanHistonesRibonucleoproteins, Small NuclearRibonucleoprotein, U7 Small NuclearRNA-Binding Protein FUSRNA, Small Nuclear

Identifiers

PMID34088960
PMCPMC8178370
OpenAlexW3164932324

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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.