Back

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.

2025-07-09 neuroscience
10.1101/2025.07.09.664014 bioRxiv
Show 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.

Matching journals

The top 4 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.