FIG. 8.

Model for exon 6D splicing regulation. A) A specific structural conformation is required for efficient splicing of exon 6D. Presence of the T nucleotide induces a secondary structure that prevents efficient utilization of the exon 6D splice sites. hnRNP H binding to GGG sequences outside exon 6D inhibits efficient splicing of the exon while SR proteins promote it. In this scenario, specific binding of hnRNP H within exon 6D does not affect splicing. The yellow circles represent the spliceosome, while red bars represent putative hnRNP H binding sites. B) The T-to-C mutation causes a conformational change in the structure of stem-loop 2. This structural change activates splicing to the exon 6D splice sites. In this case, however, hnRNP H bound to the exon 6D GGG enhances the exon splicing efficiency.