Protein modularity of alternatively spliced exons is associated with tissue-specific regulation of alternative splicing

Abstract

Recent comparative genomk analysis of alternative spiking has shown that protein moduaarsty is an important criterion for functional alternative splicing events, Exons that are alternatively spüeed in multiple organisms are much more likery to be an exact multiple of 3 nt in length, representing a class of "modular" exons that cars be inserted or removed from the transcripts without affecting the rest of the protein, To understand the precise roaes of these modular escorts, in this paper we have asiaiyzed microarray data for 3,126 alternatively spficed exons across ten mouse tissues generated by Pan and coworkers, We show that modular exons are strarsgSy associated with tissue-specific regulation of alternative splicing, Exorss that are alternatively spliced at uniformly high transcript inclusion levels or uniformly low aevels show no preference for protean modisSanty, 1rs contrast; alternatively spliced exorss with dramatic changes of inclusion levels across mouse tissues (referred to as "tissue-switched" exorss) are both strikingly biased to be modular and are strongly conserved between human and mouse, The analysis of different subsets of tissueswitched exons shows that the increased protein modularity cannot be explained by the overall exon inclusion level, but is specifically associated with tissue-switched alternative splicing. Copyright: © 2005 King and Lee.