SART3 and amyotrophic lateral sclerosis: While the precise effect of SART3 knockdown on splicing could be cell-type dependent, in general, transcript isoforms with intron retention trigger non-sense mediated decay, which leads to the downregulation of the proteins.52 Thus, perturbation of intron retention in ALS-associated genes, such as FUS, probably deregulates their balance of translation and proteostasis, which has been linked to the ALS disease.53