Fig. 7.

Schematic diagram of proposed model. a Cartoon summarising the time course of post-transcriptional events underlying human motor neurogenesis in control and VCP^mu samples. Our results suggest that the predominant RNA-processing events at an early stage of neural differentiation are IR and 3′ UTR remodelling. These events start prematurely in VCP^mu samples but do not affect major transcriptional programmes underlying human MN differentiation. b Cartoon summarising the functional consequence of aberrant IR in SFPQ gene across diverse genetic and sporadic forms of ALS. The 9 kb intron 9/9 in SFPQ is retained across all ALS-mutant backgrounds, which leads to increased cytoplasmic abundance of affected transcripts. The SFPQ protein binds extensively to the retained intron. The SFPQ protein itself is relocalised from the nucleus to the cytoplasm in all ALS-mutant backgrounds, as well as post-mortem samples of sporadic ALS patients