FIGURE 3.

Schematic of TDP-43 autoregulation and misregulation in ALS. When in nuclear excess, TDP-43 binds to a region in the 3′UTR of the TARDBP pre-mRNA leading to alternative polyadenylation and splicing; this produces mature mRNA transcripts that are subject to nonsense mediated decay. Nuclear depletion of TDP-43 as seen in ALS (right) leads to continuous upregulation of TDP-43 synthesis as more of the translated isoforms are produced.