Variation in alternative splicing across human tissues

By Gene W. Yeo, Dirk Holste, Gabriel Kreiman, C. Burge. Genome Biology, 2004

623 citations recorded by the source corpus.

BackgroundAlternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues.ResultsControlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues.ConclusionsThis study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/7228c847afc5486c01aa720cdd95a11bcd58479a

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Citations in the corpus

The MicroRNA miR-124 promotes neuronal differentiation by triggering brain-specific alternative pre-mRNA splicing. (2007, background): “Approximately half of all mammalian genes encode alternatively spliced pre-mRNAs, and a large fraction of the alternative splicing events occur exclusively in the NS (Black, 2003; Licatalosi and Darnell, 2006; Lipscombe, 2005; Maniatis and Tasic, 2002; Yeo et al., 2004).”
An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex (2014, background): “Previous expressed sequence tagged mapping studies have led to the conclusion that the brain has the highest number of alternative splicing events when compared with other organs (Yeo et al., 2004), and different brain regions are associated with complex patterns of alternative splicing (Johnson et ”
Understanding alternative splicing: towards a cellular code (2005, background): “Finally, a set of motifs associated with exons (or splice sites) that are skipped in brain or liver was found to be enriched in known silencer”
Functional and Evolutionary Insights Into Human Brain Development Through Global Transcriptome Analysis (2009, background): “Moreover, in the adult human, the brain expresses more alternatively spliced transcripts than any other tissue (Yeo et al., 2004), and the importance of specific AS programs to a number of neurodevelopmental and neurological processes has been recognized (Licatalosi and Darnell, 2006; Coutinho-Mansf”
Alternative splicing: new insights from global analyses. (2006, background): “…as the brain and testis, or from genes expressed within individual cell types that have undergone selection to provide diverse functions, such as in the immune system (Modrek et al., Cell 126, July 14, 2006 ©2006 Elsevier Inc. 39 2001; Johnson et al., 2003; Yeo et al., 2004; Watson et al., 2005).”
Past, present, and future of circRNAs (2019, neutral): “First, the brain and, more specifically, the neurons display the highest rates of alternative splicing in the body (Yeo et al , 2004; Pan et al , 2008), and circRNA biogenesis can be defined as a particular type of alternative splicing.”