Format

Send to

Choose Destination
Mol Syst Biol. 2017 Dec 14;13(12):959. doi: 10.15252/msb.20177728.

The landscape of human mutually exclusive splicing.

Author information

1
Group Systems Biology of Motor Proteins Department of NMR-Based Structural Biology Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
2
Group of Computational Systems Biology, German Center for Neurodegenerative Diseases, Göttingen, Germany.
3
Center for Molecular Neurobiology, Institute of Medical Systems Biology University Clinic Hamburg-Eppendorf, Hamburg, Germany.
4
Theoretical Computer Science and Algorithmic Methods, Institute of Computer Science Georg-August-University, Göttingen, Germany.
5
Group of Computational Systems Biology, German Center for Neurodegenerative Diseases, Göttingen, Germany sbonn@uke.de mako@nmr.mpibpc.mpg.de.
6
German Center for Neurodegenerative Diseases, Tübingen, Germany.
7
Group Systems Biology of Motor Proteins Department of NMR-Based Structural Biology Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany sbonn@uke.de mako@nmr.mpibpc.mpg.de.

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.

KEYWORDS:

alternative splicing; differential expression; mutually exclusive splicing; splicing mechanisms

PMID:
29242366
PMCID:
PMC5740500
DOI:
10.15252/msb.20177728
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center