MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development
Abstract Background Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically regulated set of cassette exons. They have key roles in nervous system development and function, as evidenced by recent results demonstrating the impact of microexons on behaviour and cognition. H...
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doaj-0d157abfd9a941beba50e1568885e8132021-01-24T12:44:23ZengBMCGenome Biology1474-760X2021-01-0122112610.1186/s13059-020-02246-2MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic developmentGuillermo E. Parada0Roberto Munita1Ilias Georgakopoulos-Soares2Hugo J. R. Fernandes3Veronika R. Kedlian4Emmanouil Metzakopian5Maria Estela Andres6Eric A. Miska7Martin Hemberg8Wellcome Sanger Institute, Wellcome Genome CampusDepartment of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de ChileWellcome Sanger Institute, Wellcome Genome CampusUK Dementia Research Institute, Department of Clinical Neurosciences, University of CambridgeWellcome Sanger Institute, Wellcome Genome CampusUK Dementia Research Institute, Department of Clinical Neurosciences, University of CambridgeDepartment of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de ChileWellcome Sanger Institute, Wellcome Genome CampusWellcome Sanger Institute, Wellcome Genome CampusAbstract Background Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically regulated set of cassette exons. They have key roles in nervous system development and function, as evidenced by recent results demonstrating the impact of microexons on behaviour and cognition. However, microexons are often overlooked due to the difficulty of detecting them using standard RNA-seq aligners. Results Here, we present MicroExonator, a novel pipeline for reproducible de novo discovery and quantification of microexons. We process 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mice. We detect 2984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons based on their inclusion patterns segregates brain tissues by developmental time, and further analysis suggests a key function for microexons in axon growth and synapse formation. Finally, we analyse single-cell RNA-seq data from the mouse visual cortex, and for the first time, we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell type-specific. Conclusions MicroExonator facilitates the investigation of microexons in transcriptome studies, particularly when analysing large volumes of data. As a proof of principle, we use MicroExonator to analyse a large collection of both mouse bulk and single-cell RNA-seq datasets. The analyses enabled the discovery of previously uncharacterized microexons, and our study provides a comprehensive microexon inclusion catalogue during mouse development.https://doi.org/10.1186/s13059-020-02246-2MicroexonsSplicingAlternative splicingNeuronal developmentSingle-cellReproducible software |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guillermo E. Parada Roberto Munita Ilias Georgakopoulos-Soares Hugo J. R. Fernandes Veronika R. Kedlian Emmanouil Metzakopian Maria Estela Andres Eric A. Miska Martin Hemberg |
spellingShingle |
Guillermo E. Parada Roberto Munita Ilias Georgakopoulos-Soares Hugo J. R. Fernandes Veronika R. Kedlian Emmanouil Metzakopian Maria Estela Andres Eric A. Miska Martin Hemberg MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development Genome Biology Microexons Splicing Alternative splicing Neuronal development Single-cell Reproducible software |
author_facet |
Guillermo E. Parada Roberto Munita Ilias Georgakopoulos-Soares Hugo J. R. Fernandes Veronika R. Kedlian Emmanouil Metzakopian Maria Estela Andres Eric A. Miska Martin Hemberg |
author_sort |
Guillermo E. Parada |
title |
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development |
title_short |
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development |
title_full |
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development |
title_fullStr |
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development |
title_full_unstemmed |
MicroExonator enables systematic discovery and quantification of microexons across mouse embryonic development |
title_sort |
microexonator enables systematic discovery and quantification of microexons across mouse embryonic development |
publisher |
BMC |
series |
Genome Biology |
issn |
1474-760X |
publishDate |
2021-01-01 |
description |
Abstract Background Microexons, exons that are ≤ 30 nucleotides, are a highly conserved and dynamically regulated set of cassette exons. They have key roles in nervous system development and function, as evidenced by recent results demonstrating the impact of microexons on behaviour and cognition. However, microexons are often overlooked due to the difficulty of detecting them using standard RNA-seq aligners. Results Here, we present MicroExonator, a novel pipeline for reproducible de novo discovery and quantification of microexons. We process 289 RNA-seq datasets from eighteen mouse tissues corresponding to nine embryonic and postnatal stages, providing the most comprehensive survey of microexons available for mice. We detect 2984 microexons, 332 of which are differentially spliced throughout mouse embryonic brain development, including 29 that are not present in mouse transcript annotation databases. Unsupervised clustering of microexons based on their inclusion patterns segregates brain tissues by developmental time, and further analysis suggests a key function for microexons in axon growth and synapse formation. Finally, we analyse single-cell RNA-seq data from the mouse visual cortex, and for the first time, we report differential inclusion between neuronal subpopulations, suggesting that some microexons could be cell type-specific. Conclusions MicroExonator facilitates the investigation of microexons in transcriptome studies, particularly when analysing large volumes of data. As a proof of principle, we use MicroExonator to analyse a large collection of both mouse bulk and single-cell RNA-seq datasets. The analyses enabled the discovery of previously uncharacterized microexons, and our study provides a comprehensive microexon inclusion catalogue during mouse development. |
topic |
Microexons Splicing Alternative splicing Neuronal development Single-cell Reproducible software |
url |
https://doi.org/10.1186/s13059-020-02246-2 |
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