Bioinformatic analysis of alternative mRNA processing
Figure 1. Alternative splicing of a hypothetical gene produces two variants, one that contains a conserved domain and another that lacks it.
Alternative splicing is a form of gene regulation which allows a single gene to produce multiple variant forms encoding different protein products. Many genes have been shown to employ alternative splicing as a mechanism for modulating gene function, and splice variants have been observed for many more.
Genes involved in regulating programmed cell death, also called apoptosis ('falling leaves' in Greek [1]), provide a notable example of a system that uses alternative splicing to generate variant forms with diverse activities [2]. For example, alternative splicing of BclX generates both pro- and anti-apoptotic variants. The pro- form is primarily expressed in short-lived cells such as lymphocytes and the anti- form is expressed in longer-lived cells such as neurons [3]. When co-expressed, the ratio between the two forms influences the cell's sensitivity to pro-apoptotic stimuli [4, 5]. Similarly striking differences between the functions of splice variants are probably common. We have found that alternative splicing disrupts or modifies conserved amino acid motifs in over 30% of multi-variant human genes, suggesting that alternative splicing frequently modifies the biological function of affected variants [6]. We found also that alternative splicing frequently changes the predicted topology of membrane-spanning regions, such as converting membrane-bound proteins to soluble forms [7].
Figure 2. Two mRNA variants encoding human tissue-type plasminogen activator (PLAT locus). Variant (a) lacks a conserved fibronectin type I motif.
We are interested in continuing this line of investigation, focusing now on fully-sequenced plant genomes, particularly the Arabidopsis genome because of its small size, available genomic resources, and highly annotated genome. Currently, we are investigating the frequency with which annotated splice variants appear in individual EST collections in an effort to gage the true variety of splice variants produced at individual loci in this important model plant species.