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Loss of nuclear TDP‐43 in amyotrophic lateral sclerosis (ALS) causes altered expression of splicing machinery and widespread dysregulation of RNA splicing in motor neurones

Loss of nuclear TDP‐43 characterizes sporadic and most familial forms of amyotrophic lateral sclerosis (ALS). TDP‐43 (encoded by TARDBP) has multiple roles in RNA processing. We aimed to determine whether (1) RNA splicing dysregulation is present in lower motor neurones in ALS and in a motor neurone‐like cell model; and (2) TARDBP mutations (mtTARDBP) are associated with aberrant RNA splicing using patient‐derived fibroblasts.