Fig. 5.

The strong cryptic 5′ss prevents U1snRNA-mediated correction in the human context. A Genomic sequence of the human OTC exon 4 exon–intron junction, with exonic and intronic nucleotides in upper and lower cases, respectively. The c.386G>A change is indicated in bold. The regions targeted by modified U1^h of the corresponding pre-mRNA are reported on top. B Splicing patterns in HepG2 transiently transfected with OTC^h-386A or OTC^h-386+5a minigenes alone or in combination with engineered U1^h, and expressed as bar plots indicating the relative percentage of each transcript. Results are expressed as mean ± SD from three independent experiments. C Splicing pattern in HepG2 or Hepa1-6 cells transiently transfected with human and mouse OTC minigenes differing at +10-11 positions alone or in combination with the corresponding U1^hOTC designed on the mutated 5′ss. Bar plots indicate the relative percentage of each transcript and results are expressed as mean ± SD from three independent experiments