Top panel shows that normal α-globin splicing is favored and cryptic splicing is suppressed when polyC-binding proteins are bound at the C-rich element downstream of exon 1. Proper splicing generates a full-length mRNA that encodes α-globin. The bottom panel depicts cryptic splicing that frequently occurs when polyC-binding proteins fail to bind. The resulting transcript cannot encode α-globin because the truncation of exon 1 will alter the translational reading frame and induce nonsense-mediated decay of the RNA. CCC, C-rich sequence; GU^cr, cryptic splice site in exon 1; GU^WT, normal splice site at the boundary between exon 1 and intron 1.