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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...

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Autores principales: Belloni, Elisa, Di Matteo, Anna, Pradella, Davide, Vacca, Margherita, Wyatt, Christopher D. R., Alfieri, Roberta, Maffia, Antonio, Sabbioneda, Simone, Ghigna, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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