Tissue-Restricted Patterns of Alternative mRNA Splicing

Since the mammalian proteome contains several fold more proteins than the number of protein-coding genes in the genome, most of these loci clearly serve as a template for multiple protein isoforms.  Alternative splicing, the pre-translational process in which different exon splice junctions are used to generate variant mRNA transcript structures, is widely recognized as a major contributor to proteome complexity.  We have used mRNA sequencing (RNA-seq) to compare expression patterns of genes and exon splice junctions across different mammalian tissues.  Genes expressed at very high levels tend to be more tissue-restricted.  Lowering the expression threshold broadens this curve and demonstrates that most protein-coding genes are transcribed in multiple tissues, a pattern consistent with many shared biological processes in all cell types.  However, on a transcriptome level, the splice junction distribution profile displays more tissue-specificity than gene loci.  Even genes that are expressed in many tissues will often encode mRNA variants that have individual exon junctions found in only a single tissue.  These highly restricted splice junctions have the potential to be sensitive molecular markers of cell type, developmental stage, and/or pathology.