GC content provides new insights into exon recognition

Studies throughout the years revealed several characteristics that differentiate alternative exons from constitutive ones. However, some of those characteristics, such as splice signals and other regulatory sequences, are inherently sequence-based. Herein we show that these characteristics are heavily biased by GC content, and may not actually differ between alternative and constitutive exons. We further examine the effect of the GC content on exon versus introns definition. We show that the GC content environment affects the way exons and introns are recognized by the splicing machinery, namely different GC contents may dictate whether mRNAs are processed via exon or intron definition.