Role of RNA decay and TDP-43 dysfunction in ALS
Transcriptome integrity and cellular homeostasis is maintained by up-frameshift protein 1 (UPF1) via controlling mRNA-decay.
The researchers in this study map UPF1-mediated RNA decay in human motor neurons and show that TDP-43 dysfunction impairs RNA surveillance.
They also show that UPF1 and TDP-43 proteins interact and co-aggregate in pathological inclusions.
The researchers demonstrate that they UPF1 and TDP-43 also coregulate alternative polyadenylation of specific transcripts extending 3′ UTRs, revealing a shared pathway underlying ALS-related RNA dysregulation.
