ArticleHuman molecular genetics2019
Disease modeling of core pre-mRNA splicing factor haploinsufficiency.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Assembly of exon junction complexes on spliceosomes begins before spliceosome activation.Nucleic acids research · 2026Article
- The RNA splicing factor PRPF8 is required for left-right organiser cilia differentiation and determination of cardiac left-right asymmetry via regulation ofbioRxiv : the preprint server for biology · 2025Article
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- A novelTranslational pediatrics · 2025Article
- Addressing the tissue specificity of U5 snRNP spliceosomopathies.Frontiers in cell and developmental biology · 2025Article
- Modeling craniofacial spliceosomopathies: a pathway toward deciphering disease mechanisms.Frontiers in cell and developmental biology · 2025Review
- A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.Disease models & mechanisms · 2024Article
- A novelFrontiers in genetics · 2024Article
- Article
- Craniofacial Defects in Embryos with Homozygous Deletion ofInternational journal of molecular sciences · 2022Article
- The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development.Journal of developmental biology · 2022Article
- MRSD: A quantitative approach for assessing suitability of RNA-seq in the investigation of mis-splicing in Mendelian disease.American journal of human genetics · 2022Article
- Over-activation of EFTUD2 correlates with tumor propagation and poor survival outcomes in hepatocellular carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Mutation in Eftud2 causes craniofacial defects in mice via mis-splicing of Mdm2 and increased P53.Human molecular genetics · 2021Article
- The Role of the U5 snRNP in Genetic Disorders and Cancer.Frontiers in genetics · 2021Review
- Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem cells.PloS one · 2020Article
- Protein Subdomain Enrichment ofFrontiers in cardiovascular medicine · 2020Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The craniofacial disorder mandibulofacial dysostosis Guion-Almeida type is caused by haploinsufficiency of the U5 snRNP gene EFTUD2/SNU114. However, it is unclear how reduced expression of this core pre-mRNA splicing factor leads to craniofacial defects. Here we use a CRISPR-Cas9 nickase strategy to generate a human EFTUD2-knockdown cell line and show that reduced expression of EFTUD2 leads to diminished proliferative ability of these cells, increased sensitivity to endoplasmic reticulum (ER) stress and the mis-expression of several genes involved in the ER stress response. RNA-Seq analysis of the EFTUD2-knockdown cell line revealed transcriptome-wide changes in gene expression, with an enrichment for genes associated with processes involved in craniofacial development. Additionally, our RNA-Seq data identified widespread mis-splicing in EFTUD2-knockdown cells. Analysis of the functional and physical characteristics of mis-spliced pre-mRNAs highlighted conserved properties, including length and splice site strengths, of retained introns and skipped exons in our disease model. We also identified enriched processes associated with the affected genes, including cell death, cell and organ morphology and embryonic development. Together, these data support a model in which EFTUD2 haploinsufficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on gene expression, including altering the expression of ER stress response genes and genes involved in the development of the craniofacial region. The increased burden of unfolded proteins in the ER resulting from mis-splicing would exceed the capacity of the defective ER stress response, inducing apoptosis in cranial neural crest cells that would result in craniofacial abnormalities during development.
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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.