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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.<\/jats:p>","DOI":"10.1038\/s41380-026-03517-3","type":"journal-article","created":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T17:02:54Z","timestamp":1772902974000},"page":"3987-4005","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Correction of eIF4E overactivation rescues translatome imbalance and core ASD-like behaviors in valproic acid-induced offspring mice"],"prefix":"10.1038","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5710-7430","authenticated-orcid":false,"given":"Miaoqi","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoyan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2173-1545","authenticated-orcid":false,"given":"Peng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanyue","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8229-2160","authenticated-orcid":false,"given":"Bin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2810-1001","authenticated-orcid":false,"given":"Wen-Cai","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6714-5023","authenticated-orcid":false,"given":"Yinghui","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-3432","authenticated-orcid":false,"given":"Lei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"3517_CR1","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1111\/jnc.13723","volume":"139","author":"SR Louros","year":"2016","unstructured":"Louros SR, Osterweil EK. 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