FIGURE 6.
Phosphomimetic substitutions at Thr-153/Tyr-155 modulate TDP-43 activity. A, schematic representation of the CFTR exon 9 mini-gene cellular reporter of TDP-43 activity. Exons and intron regions are represented as boxes and lines, respectively. TDP-43 binding to UG repeats (UG13) near the 3′ splice site inhibits exon 9 inclusion. The two major products of splicing are shown to the right. B, RNAi-resistant (siRes) TDP-43 mutants were expressed in siRNA-treated HeLa cells. Relative TDP-43 activity was calculated comparing wild-type siRes. The effect of the RNA binding-deficient mutant, F147L/F149L, was used as control. Error bars, S.D., n > 5. C, constitutively active MEK_DD, or control GFP vector, expressed in siRNA or control treated cells. Reporter activity was analyzed relative to siRes wild-type (WTsiR). Values represent the averages of independent transfection experiments. Error bars, S.D., n ≥ 4.