Production of mature mRNA transcripts in vertebrates is regulated at three stages: transcription initiation, splicing and polyadenylation. The combinatorial arrangement of variations at each stage generates, from a single gene, a variety of mRNA isoforms with different start sites, exons or 3' UTRs. Expression of Alternative Transcripts (AT) has been observed to be specific to tissue-type or developmental stage. Disruptions in expression patterns have serious consequences for an organism and are associated with numerous diseases, including cancer, multiple sclerosis, heart failure and neurodegenerative disorders. Identifying disease-specific AT's can lead to development of novel drug targets or markers. European bioinformatics laboratories have contributed to identification of variants of transcript start site, of splicing, and of polyadenylation sites. Our objective here is to develop and integrate these independent approaches in order to derive a unified view of AT formation and create a genome-scale reference database for human AT; such a data is envisaged to include alternate transcript structures, functional consequences of variations, phylogenetic conservation, and references to other major genome and proteome resources. In addition, we will seek to identify tissue- or disease-specificity of isoforms using bioinformatics approaches. This will potentially reveal co-regulated expression patterns and associated regulatory motifs involved in transcript maturation. Finally, a selection of alternative transcripts will be submitted to experimental validation using semi-quantitative RT-PCR.
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Funding SchemeSTREP - Specific Targeted Research Project