Nonsense-mediated decay masks cryptic splicing events caused by TDP-43 loss
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Nonsense-mediated decay masks cryptic splicing events caused by TDP-43 loss
Zeng, Y.; Sianto, O.; Lovchykova, A.; Liu, C.; Akiyama, T.; Petrucelli, L.; Gitler, A. D.
AbstractIn 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.