Functional importance of different patterns of correlation between adjacent cassette exons in human and mouse

Tao Peng,Xuegong Zhang,Jianning Bi,Xiaowo Wang,Yanda Li,Tingting Li,Chenghai Xue

doi:10.1186/1471-2164-9-191

Abstract

BackgroundAlternative splicing expands transcriptome diversity and plays an important role in regulation of gene expression. Previous studies focus on the regulation of a single cassette exon, but recent experiments indicate that multiple cassette exons within a gene may interact with each other. This interaction can increase the potential to generate various transcripts and adds an extra layer of complexity to gene regulation. Several cases of exon interaction have been discovered. However, the extent to which the cassette exons coordinate with each other remains unknown.ResultsBased on EST data, we employed a metric of correlation coefficients to describe the interaction between two adjacent cassette exons and then categorized these exon pairs into three different groups by their interaction (correlation) patterns. Sequence analysis demonstrates that strongly-correlated groups are more conserved and contain a higher proportion of pairs with reading frame preservation in a combinatorial manner. Multiple genome comparison further indicates that different groups of correlated pairs have different evolutionary courses: (1) The vast majority of positively-correlated pairs are old, (2) most of the weakly-correlated pairs are relatively young, and (3) negatively-correlated pairs are a mixture of old and young events.ConclusionWe performed a large-scale analysis of interactions between adjacent cassette exons. Compared with weakly-correlated pairs, the strongly-correlated pairs, including both the positively and negatively correlated ones, show more evidence that they are under delicate splicing control and tend to be functionally important. Additionally, the positively-correlated pairs bear strong resemblance to constitutive exons, which suggests that they may evolve from ancient constitutive exons, while negatively and weakly correlated pairs are more likely to contain newly emerging exons.

Highlights

Alternative splicing expands transcriptome diversity and plays an important role in regulation of gene expression
Adjacent cassette exons are a pair of cassette exons which are adjacent in the final transcript (Figure 1)
Our study focused on adjacent cassette exons because they are the simplest form of possible exon interaction and these events could be covered by sufficient ESTs

Summary

Introduction

Alternative splicing expands transcriptome diversity and plays an important role in regulation of gene expression. Previous studies focus on the regulation of a single cassette exon, but recent experiments indicate that multiple cassette exons within a gene may interact with each other. This interaction can increase the potential to generate various transcripts and adds an extra layer of complexity to gene regulation. Alternative splicing is a post-transcriptional mechanism in which the exon sequences of primary transcripts are differently included in mature RNAs. Alternative splicing is a post-transcriptional mechanism in which the exon sequences of primary transcripts are differently included in mature RNAs It expands proteomic diversity and regulates developmental or tissue-specific processes by generating multiple different transcripts (page number not for citation purposes). Many efforts have been invested in understanding the regulation of alternative splicing [1217]

Methods

Results

Discussion

Conclusion