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The switch in the predominantly expressed transcript isoform of the same gene has been identified as a significant factor in the progression of various types of cancer. These switches can impact the gain or loss of different 3'UTRs, which are hotspots for the binding of microRNAs (miRNAs) and RNA-binding proteins (RBPs). In this study, we found that in cancer-specific dominant expressing transcripts, the binding of miRNA and RBP is disrupted, suggesting that transcript switching could play a part in modulating post-transcriptional gene expression during the progression and development of cancer. Our spatial correlation analysis demonstrated that changes in miRNA and RBP binding, triggered by transcript switching, could interrupt their interplay. Additionally, statistical analysis revealed that local folding energy (LFE) is a key factor in changing miRNA and RBP interactions due to isoform switching. Overall, this study revealed that changes in cancerspecific transcripts could influence miRNA-RBP interactions due to alternations in the local RNA structure of the transcript caused by isoform switching, thereby leading to the dysregulation of crucial genes involved in the evolution and progression of cancer.
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EMBO J
September 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
During a critical period of postnatal brain development, neural circuits undergo significant refinement coincident with widespread alternative splicing of hundreds of genes, which undergo altered splice site selection for the generation of isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent phosphorylation of paxillin at its serine 119 (p-paxillin) acts as a molecular switch in the nucleus for the control of alternative splicing during this period. We show that following NMDA receptor activation, nuclear p-paxillin is recruited to nuclear speckles, where it interacts with splicing factors, such as U2AFs.
View Article and Find Full Text PDFiScience
September 2025
Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Fibroblasts can be transformed into myofibroblasts under pro-fibrotic conditions, which are characterized by increased contractility and reduced matrix degradation. The relationship between contractile activity and matrix degradation is not fully understood. To mimic physiological conditions, fibroblasts were cultured on a collagen gel with low rigidity.
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 PDFbioRxiv
August 2025
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School Boston, MA, USA.
N6-methyladenosine (m6A) is the most prevalent internal mRNA modification, enriched in the CNS yet poorly characterized in glioma. Using long-read RNA sequencing, we mapped m6A in an glioma model following knockdown (KD) of the reader IGF2BP2, writer METTL3, and eraser ALKBH5, with naive glioma cells and astrocytes as controls. Glioma cells exhibited a two-fold reduction in global m6A, suggesting progressive loss from healthy to malignant states.
View Article and Find Full Text PDFCell Death Dis
August 2025
Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Peritoneal fibrosis is a pathological alteration of the peritoneal membrane occurring in pro-inflammatory conditions, including peritoneal dialysis (PD), a renal replacement therapy. Characteristic of this process is the acquisition of invasive/pro-fibrotic abilities by mesothelial cells (MCs) through induction of mesothelial to mesenchymal transition (MMT), a cell-specific form of EMT. Long noncoding (lnc) RNAs act as major players in physiologic regulatory circuitries of the cell.
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