Evidence map›Paper›PMID 41943580›Full record

ArticleNeuron2026

DCPS modulates TDP-43-linked neurodegeneration through P-body-mediated RNA decay.

Yingzhi Ye, Zhe Zhang, Yu Xiao, Chengzhang Zhu, Noelle Wright, Julie Asbury, Yongxin Huang, Weiren Wang, Laura Gomez-Isaza, Juan C Troncoso and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026
    Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Yingzhi YeDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Physiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Zhe ZhangDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yu XiaoDepartment of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Chicago, IL 60637, USA.
Chengzhang ZhuDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Noelle WrightDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Physiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Julie AsburyDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yongxin HuangDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Cellular and Molecular Physiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Weiren WangDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Laura Gomez-IsazaDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Juan C TroncosoDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Chuan HeDepartment of Chemistry and Institute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Shuying SunDepartment of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: shuying.sun@jhmi.edu.

Funding

Transcriptome-wide base-resolution sequencing of pseudouridine in human normal and AD brain tissues-CEGS Admin supplement 2020-2021RM1HG008935 · NHGRI · UNIVERSITY OF CHICAGO · PI HE, CHUAN · 2016 to 2025
$24.4M
Single molecule study of C9ORF72 repeat RNA metabolisms in ALS/FTDRF1NS113820 · NINDS · JOHNS HOPKINS UNIVERSITY · PI SUN, SHUYING, WU, BIN · 2020 to 2025
$6.2M
Regulation mechanism and functional genomics of LINE1 RNA in TDP-43 linked neurodegenerationR01AG078948 · NIA · JOHNS HOPKINS UNIVERSITY · PI Xianjun Dong, Shuying Sun · 2022 to 2026
$4.2M
The role of m6A RNA methylation in C9ORF72-ALS/FTDR01NS127925 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Shuying Sun · 2025 to 2026
$1.2M
NHGRI NIH HHS RM1 HG008935NIA NIH HHS R01 AG078948NINDS NIH HHS R01 NS127925NINDS NIH HHS RF1 NS113820
6 · The paper itself

Abstract

The proteinopathy of the RNA-binding protein TDP-43, characterized by nuclear clearance and cytoplasmic inclusion, is a hallmark of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer's disease (AD). Through CRISPR interference (CRISPRi) screening in human neurons, we identified the decapping scavenger enzyme (DCPS) as a novel genetic modifier of TDP-43 loss-of-function (LOF)-mediated neurotoxicity. Our findings reveal that TDP-43 LOF leads to aberrant mRNA degradation via dysregulating the properties and activity of processing bodies (P-bodies). TDP-43 interacts with P-body component proteins, potentially influencing their dynamic equilibrium and assembly into ribonucleoprotein (RNP) granules. Loss of TDP-43 hyperactivates P-bodies, increasing mRNA association and RNA decay. Reducing DCPS restores P-body integrity and RNA turnover, ultimately improving neuronal survival. Overall, this study highlights a novel role of TDP-43 in RNA processing through P-body regulation and identifies DCPS as a potential therapeutic target for TDP-43 proteinopathy-related neurodegenerative diseases.

Indexed as

DNA-Binding ProteinsEndoribonucleasesNeurodegenerative DiseasesProcessing BodiesRNA StabilityAmyotrophic Lateral SclerosisAnimalsHumansNeuronsRNA, MessengerDNA-Binding ProteinsEndoribonucleasesRNA, MessengerTARDBP protein, humanALSDCPSFTDneurodegenerationP-bodyRNA decayTDP-43

Identifiers

PMID41943580
PMCPMC13058276

What OpenQuestion holds

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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.