FIGURE 6.
Htt PRR is important to the redistribution of full-length FBP11 and also the dysfunction of pre-mRNA processing. A, shown is co-localization of Htt or its mutants with FBP11 visualized by confocal fluorescence microscopy imaging. FLAG-Htt18Q, Htt100Q, or Htt100QΔP (red) and FBP11-Myc (green) were both transfected into HEK 293T cells. Scale bar = 10 μm. B, effects of Htt mutants on the splicing efficiency are shown. The data are represented as the mean ± S.E. (n = 3) and normalized to vector control. *, p < 0.001. C, redistribution of FBP11 caused by Htt100Q alters alternative splicing of the reporter minigene in a PRR-dependent manner. HEK 293T cells were transfected with a CFTR minigene construct as a reporter. The upper bands correspond to exon 9 inclusion, whereas the lower bands correspond to exon 9 skipping. The ratios from the densities of lower bands over upper bands stand for alternative splicing efficiencies. Transient transfection of Htt100Q increases exon 9 inclusion, whereas co-transfection with FBP11 can rescue the increased exon 9 inclusion caused by Htt100Q. Htt100QΔP has no effect on exon 9 inclusion compared with Htt18Q.