Unmasking the skiptic task of TDP-43

The mechanism by which mutations in TAR DNA-binding protein 43 (TDP-43) cause neurodegeneration remains incompletely understood. In this issue of The EMBO Journal, Fratta et al (2018) describe how a point mutation in the C-terminal low complexity domain of TDP-43 leads to the skipping of otherwise constitutively conserved exons. In vivo, this mutation triggers late-onset progressive neuromuscular disturbances, as seen in amyotrophic lateral sclerosis (ALS), suggesting that TDP-43 splicing gain-of-function contributes to ALS pathogenesis.

Source: EMBO Journal - June 1, 2018 Category: Molecular Biology Authors: Rouaux, C., Gonzalez De Aguilar, J.-L., Dupuis, L. Tags: Molecular Biology of Disease, Neuroscience, RNA Biology News [amp ] Views Source Type: research