Conservation of exon scrambling in human and mouse

Abstract

Exon scrambling is a phenomenon in which the exons of an mRNA transcript are spliced in an order inconsistent with that of the genome. In this thesis, I present a computational analysis of scrambled exons in human and mouse. RNA-seq data was mapped to the genome and all unaligned reads were subsequently mapped to a database of all possible exon-exon junctions. Eight conserved genes were found to undergo scrambled splicing in both species. In several cases, not only the gene was conserved, but the particular exons involved were conserved as well. Reading frame was preserved in just over half of the events, indicating that although some transcripts may be translated into protein, some may be non-functional or may play a regulatory role. The introns flanking scrambled exons were significantly longer than average, providing clues to the mechanism for this abnormal splicing pattern. The results of this study demonstrate that presence of scrambled transcripts in the cell is infrequent, but can be conserved over tens of millions of years of evolution, suggesting it has a biological function.