Sequences and splicing patterns for two of these genes for which orthologous mouse exons/genes and transcripts could be identified - the genes BHMT and CYP2C8 - are shown in detail in Figure 2b,c. In the event depicted for BHMT, the exons involved are highly conserved between the human and mouse orthologs (Figure 2b), consistent with the possibility that the splicing event may have a (conserved) regulatory role. This AS event preserves the reading frame of downstream exons, so the two isoforms are both likely to produce functional proteins, differing by the insertion/deletion of 23 amino acids. In the event depicted for CYP2C8, usage of an alternative 3' splice site removes 71 nucleotides, shifting the reading frame and leading to a premature termination codon in the exon (Figure 2c). In this case, the shorter alternative transcript is a potential substrate for nonsense-mediated decay [41,42] and the AS event may be used to regulate the level of functional mRNA/protein produced.
