Schematic model for exonization of an Alu element. (A) Alu is inserted into introns of primate genes by retrotransposition. (B) During the course of evolution, mutations within pseudo -splice sites in the intronic Alu activate these sites (black arrows). Mutations changing splicing regulatory elements are also possible (green arrow). (C) Following these mutations, part of the Alu sequence is recognized as a new exon (“exonized”), and spliced into the transcript. Typically, the Alu-containing transcript is the minor splice form, as in most cases the created splice sites are weak. Most exonizations involve the antisense orientation of the Alu sequence, presumably because of the preceding long poly-T that serves as a strong poly-pyrimidine tract necessary for the 3′SS recognition.
