Evidence map›Paper›PMID 40815569›Full record

ArticleCell reports2025

Alpha-synuclein abundance and localization are regulated by the RNA-binding protein PUMILIO1.

Maximilian Cabaj, Pietro G Mazzara, Zachary A Gaertner, Ruizhi Wang, Michaela M Pauers, Lisa K Randolph, Cláudio Gouveia Roque, Sean Feeney, Serena Raimo, Nicola de Prisco and 14 more

Abstract read
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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. ThebioRxiv : the preprint server for biology · 2026
    Article
  2. Review
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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

24 authors.

Maximilian CabajDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Pietro G MazzaraDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Zachary A GaertnerDepartment of Neurology, Northwestern University, Chicago, IL, USA.
Ruizhi WangDepartment of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Michaela M PauersDepartment of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Lisa K RandolphDoctoral Program in Neurobiology and Behavior, Columbia University, New York, NY, USA.
Cláudio Gouveia RoqueTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Sean FeeneyDoctoral Program in Neurobiology and Behavior, Columbia University, New York, NY, USA.
Serena RaimoDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Nicola de PriscoDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Alexei ChemiakineDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Xinyuan WangDivision of Movement Disorders, American Parkinson Disease Association (APDA) Center for Advanced Research and MSA Center of Excellence, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA.
Ravi K SinghDepartment of Pharmacological and Pharmaceutical Sciences, College of Pharmacy University of Houston, Houston, TX, USA.
Swetha RajasekaranDepartment of Cancer Biology and Genetics, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA.
Hari K YalamanchiliJan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX, USA; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Wayne MilesDepartment of Cancer Biology and Genetics, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA; The Ohio State University Comprehensive Cancer Center, The Ohio State University, 460 West 12th Avenue, Columbus, OH 43210, USA.
Kristin BaldwinDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Chaolin ZhangDepartment of Systems Biology, Columbia University Irving Medical Center, New York, NY, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, NY, USA.
Matthew B HarmsDepartment of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Vikram KhuranaDivision of Movement Disorders, American Parkinson Disease Association (APDA) Center for Advanced Research and MSA Center of Excellence, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Cambridge, MA, USA; Harvard Medical School, Boston, MA, USA; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Vicky BrandtDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA.
Ulrich HengstDepartment of Pathology and Cell Biology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA; Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
Rajeshwar AwatramaniDepartment of Neurology, Northwestern University, Chicago, IL, USA.
Vincenzo A GennarinoDepartment of Genetics and Development, Columbia University Irving Medical Center, New York, NY, USA; Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA; Department of Pediatrics, Columbia University Irving Medical Center, New York, NY, USA; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY, USA; Initiative for Columbia Ataxia and Tremor, Columbia University Irving Medical Center, New York, NY, USA. Electronic address: vag2138@cumc.columbia.edu.

Funding

UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
Training in the Molecular Biology of Neurodegeneration and Alzheimer's DiseaseT32AG000222 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Bruce A YANKNER · 1992 to 2026
$18.5M
NRSA Training CoreTL1TR001875 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SPANN, MARISA N, TAYLOR, JACQUELYN Y · 2016 to 2025
$8.9M
PREDOCTORAL TRAINING GRANT IN HUMAN GENETICS &DEVELOPMET32GM007088 · NIGMS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SHEN, MICHAEL M. · 1985 to 2020
$7.1M
GENETIC EPIDEMIOLOGY OF PARKINSONS DISEASER01NS036630 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MARDER, KAREN S · 1998 to 2008
$6.8M
Complexity and evolution of splicing-regulatory networksR35GM145279 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Chaolin Zhang · 2022 to 2026
$4.6M
Deciphering the Role of the Pumilio1 in Two Distinct Neurological DiseasesR01NS109858 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Vincenzo Alessandro Gennarino · 2019 to 2026
$4.1M
Investigating physiologic and pathophysiologic connections between the Parkinson's disease protein alpha-synuclein and RNA binding proteinsR01NS128142 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Vikram Khurana · 2023 to 2026
$3.3M
RNA Regulatory Networks in Neuronal Cell Type Diversity and FunctionR01NS125018 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Chaolin Zhang · 2022 to 2026
$3.0M
ADVANCED GRADUATE TRAINING PROGRAM IN NEUROBIOLOGY & BEHAVIORT32NS064928 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HENGST, ULRICH · 2010 to 2024
$3.0M
Developmental underpinnings of substantia nigra vulnerabilityR01NS119690 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI AWATRAMANI, RAJESHWAR B · 2021 to 2025
$2.4M
The translation regulation of pro-apoptotic genesR01CA251753 · NCI · OHIO STATE UNIVERSITY · PI MILES, WAYNE · 2020 to 2024
$2.0M
NCATS NIH HHS TL1 TR001875NCI NIH HHS R01 CA251753NIA NIH HHS T32 AG000222NIGMS NIH HHS K12 GM081266NIGMS NIH HHS R35 GM145279NIGMS NIH HHS T32 GM007088NIH HHS S10 OD016167NINDS NIH HHS F31 NS113574NINDS NIH HHS R01 NS036630NINDS NIH HHS R01 NS109858NINDS NIH HHS R01 NS119690NINDS NIH HHS R01 NS125018NINDS NIH HHS R01 NS128142NINDS NIH HHS R56 NS036630NINDS NIH HHS T32 NS064928
6 · The paper itself

Abstract

The protein α-synuclein, encoded by SNCA, accumulates in Parkinson's disease (PD) and other synucleinopathies for reasons that remain unclear. Here, we investigated whether SNCA is regulated in vivo by the RNA-binding protein PUM1. We establish that PUM1 binds to SNCA's 3' UTR in mouse and human cells. In induced neurons from patients with SNCA locus triplication, PUM1 mRNA levels are lower than in healthy controls, but increasing PUM1 normalizes both SNCA mRNA and α-synuclein protein levels, largely by suppressing the long 3' UTR SNCA isoform. In microfluidic chamber experiments, silencing PUM1 causes a redistribution of SNCA between the soma and axons. We also show that the previously described miR-7 regulation of SNCA mRNA requires PUM1. Lastly, we report finding several individuals with PD in clinical databases bearing variants in PUM1 that affect its RNA-binding ability. Understanding how RNA-binding proteins regulate α-synuclein could lead to viable new therapies for synucleinopathies.

Indexed as

alpha-SynucleinRNA-Binding Proteins3' Untranslated RegionsAnimalsHumansMiceMicroRNAsNeuronsParkinson DiseaseRNA, Messenger3' Untranslated Regionsalpha-SynucleinMicroRNAsPUM1 protein, humanRNA-Binding ProteinsRNA, MessengerSNCA protein, humanAGO2alpha-synucleinCP: Molecular biologyCP: NeurosciencemiR-7Parkinson’s diseasePUM1RNA-binding proteinSNCA

Identifiers

PMID40815569
PMCPMC12422362

What Socratic holds

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LicenceCC BY-NC
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 Socratic graph.