Integrating Transcriptome and Proteome Information for the Analysis of Alternative Splicing

Abstract

Summary form only given. Alternative splicing events (AS) are among the most significant factors determining the complexity of multi-cellular organisms. Most, if not all, multi-exonic human genes undergo AS. Many AS events are involved in the etiology of cancer, among many other common human disorders. The emergence of next-generation sequencing offers a unique opportunity to explore the variability generated by AS in an exhaustive way. Furthermore, recent developments in new mass-spectometry platforms have allowed a deeper survey of the human proteome. Here, an analysis of intron retention, the most rare type of AS, was performed integrating transcriptome and proteome data. Intron retention events were evaluated in relation to several features, focusing on whether they had biological significance or whether they were just spurious products from the splicing machinery. For the transcriptome analysis, the following dataset was used: 30,678 RefSeqs, 258,444 mRNAs, 6,987,423 ESTs and 9,565,439 sequences derived from NGS. For the proteome analysis, data from Geiger et al., MCP, 2012 were used. We were able to detect an intron retention event for 48% of all human genes. Confirming a previous publication from our group [1], these events are enriched at the 3'and 5'untranslated regions (UTRs). Retained introns were significantly enriched with coding potential, which supports a biological role for these events. Furthermore, they were enriched for targets of microRNAs, suggesting a role of this type of AS in the regulation of expression induced by these non-coding RNAs. A significant number of events were detected at the proteome level. This information was integrated together with transcriptome data to further explore the role of intron retention in many biological phenomena.