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

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., <i>ELP1, NEFL,</i> and <i>TMEM106B</i>) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.