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 biolog...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-12-01
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| Series: | Molecular Systems Biology |
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| Online Access: | https://doi.org/10.15252/msb.20177728 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Klas Hatje |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d02e32155ae344f0aeb8d5b8bbe64ef0 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2017-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-d02e32155ae344f0aeb8d5b8bbe64ef02025-08-20T03:46:37ZengSpringer NatureMolecular Systems Biology1744-42922017-12-01131211910.15252/msb.20177728The landscape of human mutually exclusive splicingKlas Hatje0Raza‐Ur Rahman1Ramon O Vidal2Dominic Simm3Björn Hammesfahr4Vikas Bansal5Ashish Rajput6Michel Edwar Mickael7Ting Sun8Stefan Bonn9Martin Kollmar10Group Systems Biology of Motor Proteins, Department of NMR‐Based Structural Biology, Max‐Planck‐Institute for Biophysical ChemistryGroup of Computational Systems Biology, German Center for Neurodegenerative DiseasesGroup of Computational Systems Biology, German Center for Neurodegenerative DiseasesGroup Systems Biology of Motor Proteins, Department of NMR‐Based Structural Biology, Max‐Planck‐Institute for Biophysical ChemistryGroup Systems Biology of Motor Proteins, Department of NMR‐Based Structural Biology, Max‐Planck‐Institute for Biophysical ChemistryGroup of Computational Systems Biology, German Center for Neurodegenerative DiseasesGroup of Computational Systems Biology, German Center for Neurodegenerative DiseasesGroup of Computational Systems Biology, German Center for Neurodegenerative DiseasesGroup of Computational Systems Biology, German Center for Neurodegenerative DiseasesGroup of Computational Systems Biology, German Center for Neurodegenerative DiseasesGroup Systems Biology of Motor Proteins, Department of NMR‐Based Structural Biology, Max‐Planck‐Institute for Biophysical ChemistryAbstract 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.https://doi.org/10.15252/msb.20177728alternative splicingdifferential expressionmutually exclusive splicingsplicing mechanisms |
| spellingShingle | 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 The landscape of human mutually exclusive splicing Molecular Systems Biology alternative splicing differential expression mutually exclusive splicing splicing mechanisms |
| title | The landscape of human mutually exclusive splicing |
| title_full | The landscape of human mutually exclusive splicing |
| title_fullStr | The landscape of human mutually exclusive splicing |
| title_full_unstemmed | The landscape of human mutually exclusive splicing |
| title_short | The landscape of human mutually exclusive splicing |
| title_sort | landscape of human mutually exclusive splicing |
| topic | alternative splicing differential expression mutually exclusive splicing splicing mechanisms |
| url | https://doi.org/10.15252/msb.20177728 |
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