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PRPF40B regulates NTRK2 pre-mRNA splicing to control its dominant-negative receptor, preventing BDNF signaling inhibition in neurons

GSE293518 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2026/01/28 Platform GPL18573
Summary
BDNF signaling through its receptor TRKB plays a critical role in brain development, neuroplasticity, and maintaining homeostasis. The TRKB gene, NTRK2, encodes both the full-length receptor (TRKB-FL) and a truncated isoform (TRKB-T1) generated by alternative splicing, which acts as a dominant-negative mutant, inhibiting TRKB-FL signaling. Dysregulation of BDNF-TRKB signaling, including TRKB-T1 upregulation, has been observed in neurodegenerative diseases, psychiatric disorders, and cognitive impairments. Here, we show that PRPF40B, a splicing factor associated with neuronal dysfunctions, regulates the TRKB-FL/TRKB-T1 balance during neuronal differentiation by modulating splicing. Silencing PRPF40B increases the TRKB-T1 expression, impairing neuronal differentiation and synaptic plasticity. Our data identify PRPF40B as a key regulator of the TRKB receptor balance, crucial for fine-tuning neuronal responses and preventing neuroplasticity or survival impairments.
Published in
Regulation of NTRK2 alternative splicing by PRPF40B controls neural differentiation and synaptic plasticity
Duarte-Ruiz M, Moreno-Castillo A, El Yousfi Y et al. · Cell death & disease 2025 · PMID 41360765 · doi:10.1038/s41419-025-08301-9
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Also filed as BioProject PRJNA1244863 and SRA study SRP575768. Searching any of these in the dataset finder brings you back here.

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