The landscape of human mutually exclusive splicing.

Abstract

Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA-Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi-cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila Finally, MXEs are significantly enriched in pathogenic mutations and their spatio-temporal expression might predict human disease pathology.

• Authors: Klas Hatje, Raza-Ur Rahman, Ramon O Vidal, Dominic Simm, Björn Hammesfahr, Vikas Bansal, Ashish Rajput, Michel Edwar Mickael, Ting Sun, Stefan Bonn, Martin Kollmar
• Journal: Molecular systems biology (Mol Syst Biol) Vol. 13 Issue 12 Pg. 959 (12 14 2017) ISSN: 1744-4292 [Electronic] England
• PMID: 29242366 (Publication Type: Journal Article)
• Copyright: © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Chemical References

• RNA, Messenger

Topics

• Animals
• Cluster Analysis
• Disease (genetics)
• Evolution, Molecular
• Exons (genetics)
• Genetic Loci
• Genome, Human
• Humans
• Mammals (genetics)
• Mutation (genetics)
• Protein Folding
• RNA Splicing (genetics)
• RNA, Messenger (genetics, metabolism)