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Abstract #5: Minimal conditions for exonization of intronic sequences: 5' splice site formation in alu exons. Mol Cell. 2004 Apr 23;14(2):221-31. Sorek R, Lev-Maor G, Reznik M, Dagan T, Belinky F, Graur D, Ast G.

Alu exonization, which is an evolutionary pathway that creates primate-specific transcriptomic diversity, is a powerful tool for studying alternative-splicing regulation. Through bioinformatic analyses combined with experimental methodology, we identified the mutational changes needed to create functional 5' splice sites in Alu. We revealed a complex mechanism by which the sequence composition of the 5' splice site and its base pairing with the small nuclear RNA U1 govern alternative splicing. We show that in Alu-derived GC introns the strength of the base pairing between U1 snRNA and the 5' splice site controls the skipping/inclusion ratio of alternative splicing. Based on these findings, we identified 7810 Alus within the human genome that are prone to exonization. Mutations in these Alus may cause genetic disorders or contribute to human-specific protein diversity.