Fig. 8.

Model illustrating how mutant FUS impairs NMD regulation and suppresses protein translation. (A) Normal translation and basal NMD under physiological conditions with WT FUS. (B) Mutant FUS has greater binding ability to mRNAs and associated proteins, including UPF1, leading to ribosomal stalling, translation termination, and subsequent activation of NMD. Up-regulation of pro-NMD factors (UPF1 and UPF3b) and down-regulation of the molecular brake (UPF3a) cause the loss of autoregulation and hyperactivity of NMD. pA, poly(A) tail.