Figure 2.

Regulation and different patterns of alternative splicing. (a) Alternative pre-mRNA splicing involves a complex interplay of trans-acting splicing factors with numerous cis-acting regulatory elements within the precursor mRNA sequences of eukaryotic genes. Trans-acting factors recognise and interact with different cis-acting RNA motifs present within the pre-mRNA sequence of genes; these include 5' donor and 3' acceptor sites at exon-intron boundaries; exon and intron enhancer elements (ESE, ISE), which can promote the use of specific splice sites; and exon and intron silencer elements (ESS, ISS), which when bound by proteins can repress the use of specific splice sites (adapted from [59]). (b) Different patterns of alternative splicing include: (i) normal pattern of splicing – removing introns 1, 2 and 3; (ii) whole exon exclusion – introns 1, 2 and 3, and entire exon 2 are removed; (iii) mutually exclusive exons – either exon 2 or exon 3 is removed and both exons are never retained together; (iv) intron retention – intron 2 is retained in the mRNA; and (v) cryptic splice sites – exon 2 contains a 3' cryptic splice site and exon 3 contains a 5' cryptic splice site. These compete with the native splice site to generate mRNA lacking part of an exon.