Article in bioRxiv : the preprint server for biology, 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.
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.
Kevin RhineDepartment of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0000-0003-1355-2405
Elle EpsteinDepartment of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0009-0000-0501-2041
Natasha M CarlsonDepartment of Neurobiology, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0009-0007-6504-4150
Xuezhen GeDepartment of Cell & Developmental Biology, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0009-0006-3643-235X
Orel MizrahiDepartment of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0000-0003-2189-5731
Anika KamatDepartment of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
Anita HermannDepartment of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
William R BrothersDepartment of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0000-0001-8962-7974
John RavitsDepartment of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0000-0001-6521-4649
Eric J BennettDepartment of Cell & Developmental Biology, University of California, San Diego, La Jolla, CA 92037, USA.
Gülçin PekkurnazDepartment of Neurobiology, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0000-0002-7388-6178
Gene W YeoDepartment of Cellular & Molecular Medicine, University of California, San Diego, La Jolla, CA 92037, USA.ORCID 0000-0002-0799-6037
Funding
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
Mechanisms of Prion Aggregation and Species BarriersR01NS069566 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ESKO, JEFFREY D, RAVITS, JOHN · 2011 to 2025
$5.7M
Therapeutic strategies for microsatellite expansion diseases using RNA-targeting CRISPR/CasR01NS103172 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MAURICE SCOTT SWANSON, Eugene Wei-Ming Yeo · 2017 to 2026
$5.6M
Training in Multi-Scale Analysis of Biological Structure and FunctionT32EB009380 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Andrew D. McCulloch, Padmini Rangamani · 2009 to 2026
$4.8M
Metabolic Regulation of Mitochondrial FunctionR35GM128823 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Gulcin Pekkurnaz · 2018 to 2026
$4.1M
Leveraging ubiquitin-dependent regulatory mechanisms to improve proteome quality in health and diseaseR35GM148339 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Eric J Bennett · 2023 to 2026
Neurodegenerative diseases are linked with dysregulation of the integrated stress response (ISR), which coordinates cellular homeostasis during and after stress events. Cellular stress can arise from several sources, but there is significant disagreement about which stress might contribute to aging and neurodegeneration. Here, we leverage directed transdifferentiation of human fibroblasts into aged neurons to determine the source of ISR activation. We demonstrate that increased accumulation of cytoplasmic double-stranded RNA (dsRNA) activates the eIF2α kinase PKR, which in turn triggers the ISR in aged neurons and leads to sequestration of dsRNA in stress granules. Aged neurons accumulate endogenous mitochondria-derived dsRNA that directly binds to PKR. This mitochondrial dsRNA leaks through damaged mitochondrial membranes and forms cytoplasmic foci in aged neurons. Finally, we demonstrate that PKR inhibition leads to the cessation of stress, resumption of cellular translation, and restoration of RNA-binding protein expression. Together, our results identify a source of RNA stress that destabilizes aged neurons and may contribute to neurodegeneration.
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 Socratic graph.
RNA triggers chronic stress during neuronal aging. · full record | Socratic