Tissue-specific alternative splicing at NAGNAG splice sites. Many human exons contain tandem acceptor sites (NAGNAG) that are often subject to alternative splicing. Massive parallel sequencing of tissue-derived transcriptomes now proves that this type of alternative splicing is regulated . The proximal (red) and distal (green) splice sites compete for splice site pairing. Tissue-specific splicing preferences (left and right pathways) depend on highly conserved intronic sequences within 50 bp upstream of the NAGNAG motif. The most likely features that mediate alternative NAGNAG splicing are the strength of the splice sites, the identity of the competing NAGs, the polypyrimidine tract (PPT) length and composition, and the distance between the branch point sequence and the NAGNAG motif.