Evidence map›Paper›PMID 40286269›Full record

ArticleCell reports2025

Regulation of translation elongation and integrated stress response in heat-shocked neurons.

Caitlin M Seluzicki, Milad Razavi-Mohseni, Fulya Türker, Priyal Patel, Boyang Hua, Michael A Beer, Loyal Goff, Seth S Margolis

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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.

Caitlin M SeluzickiDepartment of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Milad Razavi-MohseniDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Fulya TürkerDepartment of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey.
Priyal PatelDepartment of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Boyang HuaDepartment of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Michael A BeerDepartment of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Loyal GoffSolomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21205, USA; McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Seth S MargolisDepartment of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: smargol7@jhmi.edu.

Funding

Mechanisms Regulating Neuronal Specific Proteasomes in NeurodegenerationR01NS110754 · NINDS · JOHNS HOPKINS UNIVERSITY · PI MARGOLIS, SETH S · 2019 to 2023
$2.0M
Sequence-based Machine Learning for Inference of Dynamic Cell State Gene Network ModelsR01HG012367 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI BEER, MICHAEL A · 2022 to 2025
$1.8M
Stress Response Mechanisms Regulating Neuronal Health in the Mammalian Central Nervous System.F99AG079817 · NIA · JOHNS HOPKINS UNIVERSITY · PI SELUZICKI, CAITLIN MARIE · 2023 to 2023
$49k
NHGRI NIH HHS R01 HG012367NIA NIH HHS F99 AG079817NINDS NIH HHS R01 NS110754
6 · The paper itself

Abstract

Neurons deviate from a canonical heat shock response (HSR). Here, we revealed that neuronal adaptation to heat shock accompanies a brake on mRNA translation, slowed elongating ribosomes, phosphorylation of eukaryotic elongation factor-2 (p-eEF2), and suppressed the integrated stress response (ISR). Returning neurons to control temperature within 1 h of starting heat shock was necessary for survival and allowed for restored translation following dephosphorylation of eEF2. Subsequent to recovery, neurons briefly activated the ISR and were sensitive to the ISR inhibitor ISRIB, which enhanced protein synthesis and survival. Ribosome profiling and RNA sequencing (RNA-seq) identified newly synthesized and existing transcripts associated with ribosomes during heat shock. Preservation of these transcripts for translation during recovery was in part mediated by p-eEF2 and slowed ribosomes. Our work supports a neuronal heat shock model of a partially suspended state of translation poised for rapid reversal if recovery becomes an option and provides insight into regulation between the HSR and the ISR.

Indexed as

Heat-Shock ResponseNeuronsPeptide Chain Elongation, TranslationalAnimalsMicePeptide Elongation Factor 2PhosphorylationProtein BiosynthesisRibosomesRNA, MessengerStress, PhysiologicalPeptide Elongation Factor 2RNA, MessengerCP: Molecular biologyCP: NeuroscienceeEF2eIF2αelongationheat shockintegrated stress responseISRneuronstranslation

Identifiers

PMID40286269
PMCPMC12285177

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.