Evidence map›Paper›PMID 34496257›Full record

ArticleCell reports2021

Persistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress.

Sebastian Markmiller, Shashank Sathe, Kari L Server, Thai B Nguyen, Amit Fulzele, Neal Cody, Ashkan Javaherian, Sara Broski, Steven Finkbeiner, Eric J Bennett and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.2field-weighted citation impact, top 11% 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

26 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  3. mScience China. Life sciences · 2025
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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

12 authors at 3 institutions in 2 countries.

Sebastian MarkmillerDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92039, USA.
Shashank SatheDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92039, USA.
Kari L ServerDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92039, USA.
Thai B NguyenDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92039, USA.
Amit FulzeleDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Neal CodyInstitut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada.
Ashkan JavaherianCenter for Systems and Therapeutics, Gladstone Institutes, San Francisco, CA 94158, USA; Taube/Koret Center for Neurodegenerative Disease Research, Gladstone Institutes, San Francisco, CA 94158, USA.
Sara BroskiCenter for Systems and Therapeutics, Gladstone Institutes, San Francisco, CA 94158, USA; Taube/Koret Center for Neurodegenerative Disease Research, Gladstone Institutes, San Francisco, CA 94158, USA.
Steven FinkbeinerCenter for Systems and Therapeutics, Gladstone Institutes, San Francisco, CA 94158, USA; Taube/Koret Center for Neurodegenerative Disease Research, Gladstone Institutes, San Francisco, CA 94158, USA; Departments of Neurology and Physiology, University of California-San Francisco, San Francisco, CA 94158, USA.
Eric J BennettDivision of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Eric LécuyerInstitut de Recherches Cliniques de Montréal, Montréal, QC H2W 1R7, Canada; Département de Biochimie et Médecine Moléculaire, Université de Montréal, Montréal, QC H3C 3J7, Canada; Division of Experimental Medicine, McGill University, Montréal, QC H3A 1A3, Canada.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Stem Cell Program, University of California, San Diego, La Jolla, CA 92093, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, 92039, USA. Electronic address: geneyeo@ucsd.edu.
University of California San Diego · USGladstone Institutes · USMontreal Clinical Research Institute · CA

Funding

The proteasome in aging and neurodegenerative diseaseP01AG054407 · NIA · NORTHWESTERN UNIVERSITY · PI FINKBEINER, STEVEN M · 2018 to 2022
$14.0M
Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
Neuron and Glial Cellular Signatures from Normal and Diseased iPS Cells-SupplementU54NS091046 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI FINKBEINER, STEVEN M, FRAENKEL, ERNEST · 2014 to 2020
$11.7M
Dysfunction of the Autophagy-Lysosomal Pathway as a Common Mechanism of NeurodegenerationRF1AG058476 · NIA · J. DAVID GLADSTONE INSTITUTES · PI FINKBEINER, STEVEN M · 2017 to 2018
$4.1M
NHGRI NIH HHS R01 HG004659NIA NIH HHS P01 AG054407NIA NIH HHS RF1 AG058476NINDS NIH HHS U54 NS091046
6 · The paper itself

Abstract

Persistent cytoplasmic aggregates containing RNA binding proteins (RBPs) are central to the pathogenesis of late-onset neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). These aggregates share components, molecular mechanisms, and cellular protein quality control pathways with stress-induced RNA granules (SGs). Here, we assess the impact of stress on the global mRNA localization landscape of human pluripotent stem cell-derived motor neurons (PSC-MNs) using subcellular fractionation with RNA sequencing and proteomics. Transient stress disrupts subcellular RNA and protein distributions, alters the RNA binding profile of SG- and ALS-relevant RBPs and recapitulates disease-associated molecular changes such as aberrant splicing of STMN2. Although neurotypical PSC-MNs re-establish a normal subcellular localization landscape upon recovery from stress, cells harboring ALS-linked mutations are intransigent and display a delayed-onset increase in neuronal cell death. Our results highlight subcellular molecular distributions as predictive features and underscore the utility of cellular stress as a paradigm to study ALS-relevant mechanisms.

Indexed as

Amyotrophic Lateral SclerosisCell DeathCytoplasmic GranulesCytoplasmic Ribonucleoprotein GranulesDNA-Binding ProteinsHumansMotor NeuronsMutationRNA-Binding ProteinsRNA, MessengerDNA-Binding ProteinsRNA-Binding ProteinsRNA, Messengeramyotrophic lateral sclerosis (ALS)cellular stress responsehnRNPA2B1motor neuronsneurodegenerationnucleocytoplasmic transportprotein aggregationRNA localizationstress granulesTDP-43

Identifiers

PMID34496257
PMCPMC11341010
OpenAlexW3198114585

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.