Evidence map›Paper›PMID 38697111›Full record

ArticleNeuron2024

Epistatic interactions between NMD and TRP53 control progenitor cell maintenance and brain size.

Lin Lin, Jingrong Zhao, Naoto Kubota, Zhelin Li, Yi-Li Lam, Lauren P Nguyen, Lu Yang, Sheela P Pokharel, Steven M Blue, Brian A Yee and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Gene regulation through exon junction complex modularity.Nature structural & molecular biology · 2025
    Review
  7. The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
  8. Review
  9. Article
  10. Review
  11. 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

15 authors.

Lin LinDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA; Center for RNA Biology and Medicine, University of California, Riverside, Riverside, CA 92521, USA.
Jingrong ZhaoDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA; Center for RNA Biology and Medicine, University of California, Riverside, Riverside, CA 92521, USA.
Naoto KubotaDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA; Center for RNA Biology and Medicine, University of California, Riverside, Riverside, CA 92521, USA.
Zhelin LiDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA.
Yi-Li LamDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA; Center for RNA Biology and Medicine, University of California, Riverside, Riverside, CA 92521, USA.
Lauren P NguyenInterdepartmental Neuroscience Program, University of California, Riverside, Riverside, CA 92521, USA.
Lu YangDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Sheela P PokharelDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Steven M BlueDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Brian A YeeDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Renee ChenDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA; Institute for Genomic Medicine, University of California, San Diego, La Jolla, CA, USA.
Chun-Wei ChenDepartment of Systems Biology, Beckman Research Institute, City of Hope, Duarte, CA, USA; City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Liang ChenDepartment of Quantitative and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Sika ZhengDivision of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA; Center for RNA Biology and Medicine, University of California, Riverside, Riverside, CA 92521, USA; Interdepartmental Neuroscience Program, University of California, Riverside, Riverside, CA 92521, USA. Electronic address: sikaz@ucr.edu.

Funding

The Role of NMD in Cortical Neural Progenitor CellsR01NS125276 · NINDS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI Sika Zheng · 2022 to 2026
$2.6M
Mechanism and therapeutic opportunities of targeting the Tudor domainR01CA278050 · NCI · MAYO CLINIC ROCHESTER · PI Chun-Wei David Chen · 2023 to 2026
$2.0M
Understanding the NMD regulatory path from genetic variation to phenotypesR01GM137428 · NIGMS · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHEN, LIANG · 2020 to 2023
$1.6M
NCI NIH HHS R01 CA278050NIGMS NIH HHS R01 GM137428NINDS NIH HHS R01 NS125276
6 · The paper itself

Abstract

Mutations in human nonsense-mediated mRNA decay (NMD) factors are enriched in neurodevelopmental disorders. We show that deletion of key NMD factor Upf2 in mouse embryonic neural progenitor cells causes perinatal microcephaly but deletion in immature neurons does not, indicating NMD's critical roles in progenitors. Upf2 knockout (KO) prolongs the cell cycle of radial glia progenitor cells, promotes their transition into intermediate progenitors, and leads to reduced upper-layer neurons. CRISPRi screening identified Trp53 knockdown rescuing Upf2KO progenitors without globally reversing NMD inhibition, implying marginal contributions of most NMD targets to the cell cycle defect. Integrated functional genomics shows that NMD degrades selective TRP53 downstream targets, including Cdkn1a, which, without NMD suppression, slow the cell cycle. Trp53KO restores the progenitor cell pool and rescues the microcephaly of Upf2KO mice. Therefore, one physiological role of NMD in the developing brain is to degrade selective TRP53 targets to control progenitor cell cycle and brain size.

Indexed as

BrainMice, KnockoutNeural Stem CellsNonsense Mediated mRNA DecayTumor Suppressor Protein p53AnimalsCell CycleCyclin-Dependent Kinase Inhibitor p21Epistasis, GeneticMiceMicrocephalyRNA-Binding ProteinsCyclin-Dependent Kinase Inhibitor p21RNA-Binding ProteinsTrp53 protein, mouseTumor Suppressor Protein p53cell divisionEJCneurogenesisp21p53PAX6progenitor cell competenceTBR2Upf1Upf3aUpf3b

Identifiers

PMID38697111
PMCPMC11446168

What Socratic holds

Textmetadata
LicenceTDM
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.