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Splicing of pre-mRNAs results in the deposition of the exon junction complex (EJC) upstream of exon-exon boundaries. The EJC plays crucial post-splicing roles in export, translation, localization, and nonsense-mediated decay of mRNAs. It also aids faithful splicing of pre-mRNAs containing large introns, albeit via an unknown mechanism. Here, we show that the core EJC plus the accessory factors RnpS1 and Acinus aid in definition and efficient splicing of neighboring introns. This requires prior deposition of the EJC in close proximity to either an upstream or downstream splicing event. If present in isolation, EJC-dependent introns are splicing-defective also in wild-type cells. Interestingly, the most affected intron belongs to the piwi locus, which explains the reported transposon desilencing in EJC-depleted Drosophila ovaries. Based on a transcriptome-wide analysis, we propose that the dependency of splicing on the EJC is exploited as a means to control the temporal order of splicing events.
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http://dx.doi.org/10.1101/gad.245738.114 | DOI Listing |
Front Endocrinol (Lausanne)
September 2025
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Introduction: Triple A syndrome (OMIM*231550) is a rare autosomal recessive disorder characterized by achalasia, alacrima, adrenal insufficiency, and neurological features. It is caused by functional impairment of the nucleoporin ALADIN due to mutations in the gene. Limited data exists on triple A syndrome from Sub-Saharan African and Arab countries.
View Article and Find Full Text PDFCell Rep
September 2025
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA; Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA. Electronic address:
Progranulin-deficient frontotemporal dementia (GRN-FTD) is a major cause of familial FTD with TAR DNA-binding protein 43 (TDP-43) pathology, which is linked to exon dysregulation. However, little is known about this dysregulation in glial and neuronal cells. Here, using splice-junction-covering enrichment probes, we introduce single-nuclei long-read RNA sequencing 2 (SnISOr-Seq2), targeting 3,630 high-interest genes without loss of precision, and complete the first single-cell, long-read-resolved case-control study for neurodegeneration.
View Article and Find Full Text PDFDev Biol
September 2025
Department of Orthopedics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address:
Thrombocytopenia-Absent Radius (TAR) syndrome is a rare congenital condition with reduced platelets, forelimb anomalies, and variable heart and kidney defects. TAR syndrome is caused by mutations in RBM8A/Y14, a component of the exon junction complex. How perturbing a general mRNA-processing factor causes the selective TAR Syndrome phenotypes remains unknown.
View Article and Find Full Text PDFBiochem Biophys Res Commun
August 2025
RNA-Binding Proteins Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, India. Electronic address:
The Exon-Junction Complex (EJC) is essential for post-transcriptional gene regulation, with MAGOH as one of its core components, known for its involvement in mRNA surveillance and translation. In this study, we characterize an evolutionarily conserved, alternatively spliced isoform of MAGOH, i.e.
View Article and Find Full Text PDFHum Genomics
August 2025
Department of Endocrinology, Genetics and Metabolism, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, 272029, Shandong, PR China.
Backgroud: Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous group of inherited connective tissue disorder. This investigation aims to elucidate the molecular etiology underlying a four-generation Chinese family affected by OI.
Methods: Whole-exome sequencing was employed to identify pathogenic variants in the proband, with subsequent Sanger sequencing performed for familial co-segregation analysis.