An intronic signal for alternative splicing in the human genome

• Published in: PloS one 2007-11, Vol.2 (11), p.e1246-e1246
• Main Authors: Havlioglu, Necat, Wang, Jun, Fushimi, Kazuo, Vibranovski, Maria D, Kan, Zhengyan, Gish, Warren, Fedorov, Alexei, Long, Manyuan, Wu, Jane Y
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Analysis; Apoptosis; Binding sites; Bioinformatics; Caenorhabditis; Cancer; Caspase; Caspase 2 - genetics; Caspase-2; Cell Biology/Gene Expression; Cell death; Cloning; Computational Biology/Alternative Splicing; Computer applications; Evolution; Exon skipping; Expressed Sequence Tags; Gene expression; Genes; Genetic aspects; Genome, Human; Genomes; Genomics; Humans; Introns; Medicine; Molecular Biology/Bioinformatics; Molecular Biology/RNA Splicing; Nucleotide sequence; Ontology; Polymerase chain reaction; Proteins; Regulation; Regulatory Sequences, Nucleic Acid; Sequences
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0001246

An important level at which the expression of programmed cell death (PCD) genes is regulated is alternative splicing. Our previous work identified an intronic splicing regulatory element in caspase-2 (casp-2) gene. This 100-nucleotide intronic element, In100, consists of an upstream region containing a decoy 3' splice site and a downstream region containing binding sites for splicing repressor PTB. Based on the signal of In100 element in casp-2, we have detected the In100-like sequences as a family of sequence elements associated with alternative splicing in the human genome by using computational and experimental approaches. A survey of human genome reveals the presence of more than four thousand In100-like elements in 2757 genes. These In100-like elements tend to locate more frequent in intronic regions than exonic regions. EST analyses indicate that the presence of In100-like elements correlates with the skipping of their immediate upstream exons, with 526 genes showing exon skipping in such a manner. In addition, In100-like elements are found in several human caspase genes near exons encoding the caspase active domain. RT-PCR experiments show that these caspase genes indeed undergo alternative splicing in a pattern predicted to affect their functional activity. Together, these results suggest that the In100-like elements represent a family of intronic signals for alternative splicing in the human genome.