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Correction of eIF4E overactivation rescues translatome imbalance and core ASD-like behaviors in valproic acid-induced offspring mice.

Overview

Authors: Miaoqi Huang1,2,3,4, Han Ye1,2, Yong Xu1,2, Jiaoyan Xie1,2, Xinyu Wang1,2, Yan Luo1,2, Peng Liu1,2, Xuanyue Ma1,2, Shiqing Zhang1,2, Bin Jiang3,4, Wen-Cai Ye1,2, Yinghui Peng1,2, Lei Shi1,2
ORCID iDs: Miaoqi Huang, Peng Liu, Bin Jiang, Wen-Cai Ye, Yinghui Peng, Lei Shi
  1. State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Guangzhou, 510632 China
  2. JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Guangdong Hong Kong-Macau Joint Laboratory for Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632 Guangdong China
  3. Medical College, Jiaying University, Meizhou, 514031 Guangdong China
  4. Guangdong Province Key Laboratory of Brain Function and Disease, School of Medicine, Sun Yat-sen University, Shenzhen, 518107 China
Institutions: Sun Yat-sen University (China); Jinan University (China); Jiaying University (China)
Journal: Molecular psychiatry, volume 31, issue 7, pages 3987-4005
Dates: received 15 July 2025; accepted 18 February 2026; published online 7 March 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41380-026-03517-3 · PMID 41795048 · PMCID PMC13269136 · OpenAlex W7134168644
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: mouse (organism), autism (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Autism spectrum disorders, Neuroscience
MeSH: Autism Spectrum Disorder*, Eukaryotic Initiation Factor-4E*, Animals, Behavior, Animal, Cerebral Cortex, Disease Models, Animal, Female, Male, Mice, Mice, Inbred C57BL, Mitochondria, Phosphorylation, Pregnancy, Prenatal Exposure Delayed Effects, Protein Biosynthesis, Ribosomes, Valproic Acid (* major topic)
Topic: Autism Spectrum Disorder Research (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: National Natural Science Foundation of China (National Science Foundation of China) (82371175, 82401804, 82101614, U24A20804)
Citations: cited by 1 paper (Europe PMC); 86 references in the paper

Abstract

Perturbed protein synthesis plays a crucial role in the pathogenesis of autism spectrum disorder (ASD), but the altered translational pattern and underlying mechanism remain poorly understood. Here, we identified an exaggeration of global protein synthesis in the cerebral cortex of offspring mice following prenatal exposure of valproic acid (VPA), a well-established ASD model. Integrative analysis of polyribosome-based translatome and proteome data revealed remarkable upregulation of ribosomal and mitochondrial genes in VPA-exposed cortex at both translational and protein levels, but not transcriptional levels. Further analysis pinpoints that overactivation of the translation initiation factor eIF4E causes the aberrant translatome and mitochondrial impairments in VPA-exposed cortex. Pharmacological inhibition of eIF4E phosphorylation during juvenile displayed persistent effectiveness in mitigating ASD-like social deficits and stereotyped behavior in VPA mice until adulthood. Collectively, these findings demonstrate that eIF4E overactivation leads to imbalanced protein synthesis that favors translation of ribosomal and mitochondrial genes, causing core ASD-like behaviors.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

No dataset and no data link were found in the paper.

Data availability

The raw sequencing data generated in this study have been deposited in the Genome Sequence Archive (GSA) at the National Genomics Data Center (NGDC), China National Center for Bioinformation / Beijing Institute of Genomics, Chinese Academy of Sciences, under accession numbers CRA037712 and CRA037713. The data are associated with BioProject PRJCA056529 and are publicly accessible at https://ngdc.cncb.ac.cn/gsa/. The analysis codes of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 13 authors, 2 keywords, 17 MeSH terms, 1 funder, 86 references.

Cite

This paper

Huang, M., Ye, H., Xu, Y., Xie, J., Wang, X., Luo, Y., Liu, P., Ma, X., Zhang, S., Jiang, B., Ye, W.-C., Peng, Y., & Shi, L. (2026). Correction of eIF4E overactivation rescues translatome imbalance and core ASD-like behaviors in valproic acid-induced offspring mice. Molecular psychiatry, 31(7), 3987-4005. https://doi.org/10.1038/s41380-026-03517-3

BibTeX

@article{huang2026correction,
author = {Huang, Miaoqi and Ye, Han and Xu, Yong and Xie, Jiaoyan and Wang, Xinyu and Luo, Yan and Liu, Peng and Ma, Xuanyue and Zhang, Shiqing and Jiang, Bin and Ye, Wen-Cai and Peng, Yinghui and Shi, Lei},
title = {{Correction of eIF4E overactivation rescues translatome imbalance and core ASD-like behaviors in valproic acid-induced offspring mice}},
journal = {Molecular psychiatry},
year = {2026},
month = mar,
volume = {31},
number = {7},
pages = {3987--4005},
publisher = {Springer Nature},
issn = {1359-4184},
doi = {10.1038/s41380-026-03517-3},
url = {https://doi.org/10.1038/s41380-026-03517-3},
pmid = {41795048},
pmcid = {PMC13269136}
}

RIS

TY - JOUR
AU - Huang, Miaoqi
AU - Ye, Han
AU - Xu, Yong
AU - Xie, Jiaoyan
AU - Wang, Xinyu
AU - Luo, Yan
AU - Liu, Peng
AU - Ma, Xuanyue
AU - Zhang, Shiqing
AU - Jiang, Bin
AU - Ye, Wen-Cai
AU - Peng, Yinghui
AU - Shi, Lei
TI - Correction of eIF4E overactivation rescues translatome imbalance and core ASD-like behaviors in valproic acid-induced offspring mice
T2 - Molecular psychiatry
J2 - Mol Psychiatry
PY - 2026
DA - 2026/03/07
VL - 31
IS - 7
SP - 3987
EP - 4005
SN - 1359-4184
PB - Springer Nature
DO - 10.1038/s41380-026-03517-3
UR - https://doi.org/10.1038/s41380-026-03517-3
LA - en
ER -

CSL-JSON

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