Evo Devo

Evolutionary development - at the biological interface between genetic regulatory mechanisms and biological evolution.

alternative 5' splicing

The alternative donor 5' site operates in or other of two mechanisms to alter the protein product. Alternative splicing of internal exons can generate cassette, alternative 5' splice sites, alternative 3' splice sites, intron retention, and mutually exclusive splicing.

Due to alternative promoters, selection of one of several possible first exons results in variability at the 5' terminus of the mRNA. The determinative regulatory step in this mechanism is operation of a promoter rather than splice-site selection. The effect on the coding potential depends on the location of the translation initiation codon:
1. If translation initiates close to the first exons, the encoded proteins will contain alternative N termini.
2. If translation initiates in the common exon, different mRNAs will be generated that contain different 5' untranslated regions but that encode identical proteins.

Variation in alternative splicing across human tissues.
Controlling 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.
Gene Yeo, Dirk Holste, Gabriel Kreiman and Christopher B Burge Free Full Text Variation in alternative splicing across human tissues. Genome Biology 2004, 5:R74


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