Evidence map›Paper›PMID 42786260›Full record

ArticleMolecular psychiatry2026

Disrupted PQBP1-HNRNPU-LINE-1 axis underlies aberrant neurodevelopment in renpenning syndrome.

Jinyu Zhang, Wenzheng Qu, Xuejun Cheng, Lan Li, Ying Li, Shilong Li, Lei Ye, Lin Yu, Yun Li, Peifang Jiang and 5 more

Abstract read
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In one paragraph

Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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3 · Its place in the literature

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0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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.

Jinyu Zhang *Department of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Wenzheng Qu *Department of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Xuejun ChengDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Lan LiDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Ying LiDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Shilong LiDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Lei YeDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.ORCID http://orcid.org/0009-0000-0050-4397
Lin YuDepartment of Pediatrics, The Fourth Affiliated Hospital of School of Medicine, and International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, 322000, China.
Yun LiThe Hospital for Sick Children, 686 Bay Street, Toronto, ON, M5G 0A4, Canada.ORCID http://orcid.org/0000-0002-5849-5910
Peifang JiangDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Xiling JiangAffiliated Hospital of Chifeng University, Chifeng, 024000, China.
Jun XuDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.ORCID http://orcid.org/0009-0001-1360-2778
Chaochun ZouDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.ORCID http://orcid.org/0000-0002-4667-3636
Qiang ShuDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China.
Xuekun LiDepartment of Neurology, Department of Genetics and Metabolism, Department of Endocrinology, Department of Thoracic and Cardiovascular Surgery, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Children and Adolescents' Health and Disease, Hangzhou, 310052, China. xuekun_li@zju.edu.cn.ORCID http://orcid.org/0000-0002-6985-6363

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82361148724National Natural Science Foundation of China (National Science Foundation of China) 82571341, 82371182Natural Science Foundation of Zhejiang Province (Zhejiang Provincial Natural Science Foundation) LD25H090001
6 · The paper itself

Abstract

Mutations in RNA splicing factor PQBP1 cause Renpenning syndrome (RS), yet whether LINE-1 (L1) contributes to RS pathogenesis remains unclear. Here, we generated human forebrain organoids model carrying a novel patient-derived PQBP1 variant (c.28 C > G; p.R10G), and observed impaired neurogenesis in RS organoids. Bulk and single-cell RNA-sequencing revealed that PQBP1 R10G mutation upregulated evolutionarily ancient L1 expression and induced aberrant L1 splicing, resulting in the redundant production of non-canonical L1-containing transcripts. Mechanistically, disrupted PQBP1-HNRNPU interaction by PQBP1 R10G mutation impaired U1/U2 small nuclear ribonucleoprotein (snRNP) recruitment to splicing sites, leading to increased L1-containing intron retention of neurodevelopmental genes, including WDR11. L1 retention reduced canonical WDR11 transcripts and consequently protein expression. Canonical WDR11, not L1-containing isoform, ameliorated the neurodevelopmental deficits of RS organoids. Together, our findings establish the dysregulated PQBP1-HNRNPU-L1 axis as a pathogenic driver of RS and nominate WDR11 as a potential therapeutic target for RS.

Identifiers

PMID42786260

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