bioRxiv [Preprint]. 2025 Jul 9:2025.07.09.664014. doi: 10.1101/2025.07.09.664014.
ABSTRACT
In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is lost from the nucleus, leading to cryptic exon inclusion events in dozens of neuronal genes. Here, we show that many cryptic splicing events have been missed by standard RNA-sequencing analyses because they are substrates for nonsense-mediated decay. By inhibiting nonsense-mediated decay in neurons we unmask hundreds of novel cryptic splicing events caused by TDP-43 depletion, providing a new picture to TDP-43 loss of function in neurons.
PMID:40672339 | PMC:PMC12265704 | DOI:10.1101/2025.07.09.664014