Interference of nuclear speckles: A nexus of RNA foci, dipeptide repeats, and mis-splicing in C9ORF72 ALS/FTD.

In this issue of Neuron, Wu et al.1 show that nuclear speckle proteins are sequestered by both nuclear RNA foci and cytoplasmic dipeptide repeat aggregates in C9ORF72-ALS/FTD. Consequently, dysregulation of splicing induces widespread splicing alterations and contributes to neurodegeneration.