ArticlePLoS genetics2016
Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly.
Article in PLoS genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 108 citations in OpenAlex.
- Beyond quality control: biological roles of nonsense-mediated RNA decay.The EMBO journal · 2026Review
- Chemical inhibition of exon junction complex assembly impairs mRNA localization and neural stem cells ciliogenesis.Nucleic acids research · 2025Article
- Impaired cortical development and translational control in a missense mouse model of DDX3X syndrome.Disease models & mechanisms · 2025Article
- Mutations in the spliceosomal gene SNW1 cause neurodevelopment disorders with microcephaly.The Journal of clinical investigation · 2025Article
- Biological roles of nonsense-mediated RNA decay: insights from the nervous system.Current opinion in genetics & development · 2025Review
- DEAD/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders.Trends in genetics : TIG · 2025Review
- Fine-tuning of Wnt signaling by RNA surveillance factor Smg5 in the mouse craniofacial development.iScience · 2025Article
- mRNA stability fine-tunes gene expression in the developing cortex to control neurogenesis.PLoS biology · 2025Article
- The RNA-binding protein EIF4A3 promotes axon development by direct control of the cytoskeleton.Cell reports · 2024Article
- Epistatic interactions between NMD and TRP53 control progenitor cell maintenance and brain size.Neuron · 2024Article
- Role of Hsa_circ_0000880 in the Regulation of High Glucose-Induced Apoptosis of Retinal Microvascular Endothelial Cells.Translational vision science & technology · 2024Article
- Article
- Aberrant generation of dentate gyrus granule cells is associated with epileptic susceptibility in p53 conditional knockout mice.Frontiers in neuroscience · 2024Article
- The exon junction complex component EIF4A3 is essential for mouse and human cortical progenitor mitosis and neurogenesis.Development (Cambridge, England) · 2023Article
- Transcriptomic Analyses of Brains of RBM8A Conditional Knockout Mice at Different Developmental Stages Reveal Conserved Signaling Pathways Contributing to Neurodevelopmental Diseases.International journal of molecular sciences · 2023Article
- Exon architecture controls mRNA mScience (New York, N.Y.) · 2023Article
- P53 independent pathogenic mechanisms contribute to BubR1 microcephaly.Frontiers in cell and developmental biology · 2023Article
- DNA damage and repair: underlying mechanisms leading to microcephaly.Frontiers in cell and developmental biology · 2023Review
- The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes.RNA biology · 2023Article
- Prenatal alcohol exposure results in brain region- and sex-specific changes inFrontiers in neuroscience · 2023Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The exon junction complex (EJC) is an RNA binding complex comprised of the core components Magoh, Rbm8a, and Eif4a3. Human mutations in EJC components cause neurodevelopmental pathologies. Further, mice heterozygous for either Magoh or Rbm8a exhibit aberrant neurogenesis and microcephaly. Yet despite the requirement of these genes for neurodevelopment, the pathogenic mechanisms linking EJC dysfunction to microcephaly remain poorly understood. Here we employ mouse genetics, transcriptomic and proteomic analyses to demonstrate that haploinsufficiency for each of the 3 core EJC components causes microcephaly via converging regulation of p53 signaling. Using a new conditional allele, we first show that Eif4a3 haploinsufficiency phenocopies aberrant neurogenesis and microcephaly of Magoh and Rbm8a mutant mice. Transcriptomic and proteomic analyses of embryonic brains at the onset of neurogenesis identifies common pathways altered in each of the 3 EJC mutants, including ribosome, proteasome, and p53 signaling components. We further demonstrate all 3 mutants exhibit defective splicing of RNA regulatory proteins, implying an EJC dependent RNA regulatory network that fine-tunes gene expression. Finally, we show that genetic ablation of one downstream pathway, p53, significantly rescues microcephaly of all 3 EJC mutants. This implicates p53 activation as a major node of neurodevelopmental pathogenesis following EJC impairment. Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease.
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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 OpenQuestion graph.