An analysis of tissue-specific alternative splicing at the protein level.

The role of alternative splicing is one of the great unanswered questions in cellular biology. There is strong evidence for alternative splicing at the transcript level, and transcriptomics experiments show that many splice events are tissue specific. It has been suggested that alternative splicing...

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Main Authors: Jose Manuel Rodriguez, Fernando Pozo, Tomas di Domenico, Jesus Vazquez, Michael L Tress
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-10-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1008287
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author Jose Manuel Rodriguez
Fernando Pozo
Tomas di Domenico
Jesus Vazquez
Michael L Tress
author_facet Jose Manuel Rodriguez
Fernando Pozo
Tomas di Domenico
Jesus Vazquez
Michael L Tress
author_sort Jose Manuel Rodriguez
collection DOAJ
description The role of alternative splicing is one of the great unanswered questions in cellular biology. There is strong evidence for alternative splicing at the transcript level, and transcriptomics experiments show that many splice events are tissue specific. It has been suggested that alternative splicing evolved in order to remodel tissue-specific protein-protein networks. Here we investigated the evidence for tissue-specific splicing among splice isoforms detected in a large-scale proteomics analysis. Although the data supporting alternative splicing is limited at the protein level, clear patterns emerged among the small numbers of alternative splice events that we could detect in the proteomics data. More than a third of these splice events were tissue-specific and most were ancient: over 95% of splice events that were tissue-specific in both proteomics and RNAseq analyses evolved prior to the ancestors of lobe-finned fish, at least 400 million years ago. By way of contrast, three in four alternative exons in the human gene set arose in the primate lineage, so our results cannot be extrapolated to the whole genome. Tissue-specific alternative protein forms in the proteomics analysis were particularly abundant in nervous and muscle tissues and their genes had roles related to the cytoskeleton and either the structure of muscle fibres or cell-cell connections. Our results suggest that this conserved tissue-specific alternative splicing may have played a role in the development of the vertebrate brain and heart.
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spelling doaj.art-e14382a062824186b48ee03bf6faf5f62022-12-21T18:43:38ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582020-10-011610e100828710.1371/journal.pcbi.1008287An analysis of tissue-specific alternative splicing at the protein level.Jose Manuel RodriguezFernando PozoTomas di DomenicoJesus VazquezMichael L TressThe role of alternative splicing is one of the great unanswered questions in cellular biology. There is strong evidence for alternative splicing at the transcript level, and transcriptomics experiments show that many splice events are tissue specific. It has been suggested that alternative splicing evolved in order to remodel tissue-specific protein-protein networks. Here we investigated the evidence for tissue-specific splicing among splice isoforms detected in a large-scale proteomics analysis. Although the data supporting alternative splicing is limited at the protein level, clear patterns emerged among the small numbers of alternative splice events that we could detect in the proteomics data. More than a third of these splice events were tissue-specific and most were ancient: over 95% of splice events that were tissue-specific in both proteomics and RNAseq analyses evolved prior to the ancestors of lobe-finned fish, at least 400 million years ago. By way of contrast, three in four alternative exons in the human gene set arose in the primate lineage, so our results cannot be extrapolated to the whole genome. Tissue-specific alternative protein forms in the proteomics analysis were particularly abundant in nervous and muscle tissues and their genes had roles related to the cytoskeleton and either the structure of muscle fibres or cell-cell connections. Our results suggest that this conserved tissue-specific alternative splicing may have played a role in the development of the vertebrate brain and heart.https://doi.org/10.1371/journal.pcbi.1008287
spellingShingle Jose Manuel Rodriguez
Fernando Pozo
Tomas di Domenico
Jesus Vazquez
Michael L Tress
An analysis of tissue-specific alternative splicing at the protein level.
PLoS Computational Biology
title An analysis of tissue-specific alternative splicing at the protein level.
title_full An analysis of tissue-specific alternative splicing at the protein level.
title_fullStr An analysis of tissue-specific alternative splicing at the protein level.
title_full_unstemmed An analysis of tissue-specific alternative splicing at the protein level.
title_short An analysis of tissue-specific alternative splicing at the protein level.
title_sort analysis of tissue specific alternative splicing at the protein level
url https://doi.org/10.1371/journal.pcbi.1008287
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