A trio of unique alternative splicing patterns : the splicing of tandem NAGNAG acceptors, transcription-start-site-dependent and mutually dependent cassette exons

Abstract

With the rapid increase in the volume of genomic and transcript data in mouse and human, a diverse set of alternative splicing patterns can be discovered. We have set out to explore in more depth some of these unique splicing patterns which include: i.) tandem acceptor splice sites termed ’NAGNAGs’, which cause an exon length variation of three nucleotides, ii.) the splicing of internal cassette exons, whose inclusion and exclusion are strongly associated with their transcriptional start sites, iii.) and groups of internal cassette exons that are always observed to be either included or excluded together within a transcript. We did not find much evidence of functional potential for the majority of variant acceptor splice sites carrying the NAGNAG motif and thus conclude that their abundance is due mostly to the stochastic behaviour of the spliceosome. We inferred that a large fraction (15-30%) of internal cassette exons in transcription units with multiple start sites are included and skipped in a transcription-start-site-dependent manner. We did not find that this relationship is conserved in orthologous human and mouse exons. Our first analysis has revealed several interesting trends in mutually dependent exons when compared to mutually exclusive and constitutive exons: these exons have a stronger pressure to maintain the reading frame as a group of exons rather than individually, and they generally have shorter intron lengths. Ours are the first analyses of transcription-start-site-dependent and mutually-dependent splicing. Their mechanisms remain to be further elucidated and our results provide a good starting point for future computational and experimental studies.