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Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells
Alternative splicing (AS) plays an important role in expanding the complexity of the human genome through the production of specialized proteins regulating organ development and physiological functions, as well as contributing to several pathological conditions. How AS programs impact on the signali...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953062/ https://www.ncbi.nlm.nih.gov/pubmed/31771184 http://dx.doi.org/10.3390/cells8121498 |
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author | Belloni, Elisa Di Matteo, Anna Pradella, Davide Vacca, Margherita Wyatt, Christopher D. R. Alfieri, Roberta Maffia, Antonio Sabbioneda, Simone Ghigna, Claudia |
author_facet | Belloni, Elisa Di Matteo, Anna Pradella, Davide Vacca, Margherita Wyatt, Christopher D. R. Alfieri, Roberta Maffia, Antonio Sabbioneda, Simone Ghigna, Claudia |
author_sort | Belloni, Elisa |
collection | PubMed |
description | Alternative splicing (AS) plays an important role in expanding the complexity of the human genome through the production of specialized proteins regulating organ development and physiological functions, as well as contributing to several pathological conditions. How AS programs impact on the signaling pathways controlling endothelial cell (EC) functions and vascular development is largely unknown. Here we identified, through RNA-seq, changes in mRNA steady-state levels in ECs caused by the neuro-oncological ventral antigen 2 (Nova2), a key AS regulator of the vascular morphogenesis. Bioinformatics analyses identified significant enrichment for genes regulated by peroxisome proliferator-activated receptor-gamma (Ppar-γ) and E2F1 transcription factors. We also showed that Nova2 in ECs controlled the AS profiles of Ppar-γ and E2F dimerization partner 2 (Tfdp2), thus generating different protein isoforms with distinct function (Ppar-γ) or subcellular localization (Tfdp2). Collectively, our results supported a mechanism whereby Nova2 integrated splicing decisions in order to regulate Ppar-γ and E2F1 activities. Our data added a layer to the sequential series of events controlled by Nova2 in ECs to orchestrate vascular biology. |
format | Online Article Text |
id | pubmed-6953062 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69530622020-01-23 Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells Belloni, Elisa Di Matteo, Anna Pradella, Davide Vacca, Margherita Wyatt, Christopher D. R. Alfieri, Roberta Maffia, Antonio Sabbioneda, Simone Ghigna, Claudia Cells Article Alternative splicing (AS) plays an important role in expanding the complexity of the human genome through the production of specialized proteins regulating organ development and physiological functions, as well as contributing to several pathological conditions. How AS programs impact on the signaling pathways controlling endothelial cell (EC) functions and vascular development is largely unknown. Here we identified, through RNA-seq, changes in mRNA steady-state levels in ECs caused by the neuro-oncological ventral antigen 2 (Nova2), a key AS regulator of the vascular morphogenesis. Bioinformatics analyses identified significant enrichment for genes regulated by peroxisome proliferator-activated receptor-gamma (Ppar-γ) and E2F1 transcription factors. We also showed that Nova2 in ECs controlled the AS profiles of Ppar-γ and E2F dimerization partner 2 (Tfdp2), thus generating different protein isoforms with distinct function (Ppar-γ) or subcellular localization (Tfdp2). Collectively, our results supported a mechanism whereby Nova2 integrated splicing decisions in order to regulate Ppar-γ and E2F1 activities. Our data added a layer to the sequential series of events controlled by Nova2 in ECs to orchestrate vascular biology. MDPI 2019-11-23 /pmc/articles/PMC6953062/ /pubmed/31771184 http://dx.doi.org/10.3390/cells8121498 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Belloni, Elisa Di Matteo, Anna Pradella, Davide Vacca, Margherita Wyatt, Christopher D. R. Alfieri, Roberta Maffia, Antonio Sabbioneda, Simone Ghigna, Claudia Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells |
title | Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells |
title_full | Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells |
title_fullStr | Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells |
title_full_unstemmed | Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells |
title_short | Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells |
title_sort | gene expression profiles controlled by the alternative splicing factor nova2 in endothelial cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953062/ https://www.ncbi.nlm.nih.gov/pubmed/31771184 http://dx.doi.org/10.3390/cells8121498 |
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