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TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes

Zeng, Y.; Lovchykova, A.; Aikyama, T.; Liu, C.; Guo, C.; Jawahar, V. M.; Sianto, O.; Calliari, A.; Prudencio, M.; Dickson, D. W.; Petrucelli, L.; Gitler, A. D.

2024-01-22 neuroscience
10.1101/2024.01.22.575730 bioRxiv
Show abstract

In frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is depleted from the nucleus. TDP-43 loss leads to cryptic exon inclusion but a role in other RNA processing events remains unresolved. Here, we show that loss of TDP-43 causes widespread changes in alternative polyadenylation, impacting expression of disease-relevant genes (e.g., ELP1, NEFL, and TMEM106B) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.

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