TDP-43 loss brings RNA to a twist ending

Nature Neuroscience, Published online: 21 October 2025; doi:10.1038/s41593-025-02065-3

In amyotrophic lateral sclerosis (ALS), nuclear depletion and cytoplasmic aggregation of the RNA-binding protein TDP-43 cause widespread dysregulation of mRNA splicing. Two recent studies have now revealed that loss of TDP-43 also affects mRNA 3′ end cleavage and polyadenylation, further influencing mRNA metabolism and protein expression.