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Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells

Belloni, E; Di Matteo, A; Pradella, D; Vacca, M; Wyatt, CDR; Alfieri, R; Maffia, A; ... Ghigna, C; + view all (2019) Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells. Cells , 8 (12) 10.3390/cells8121498. Green open access

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Abstract

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.

Type: Article
Title: Gene Expression Profiles Controlled by the Alternative Splicing Factor Nova2 in Endothelial Cells
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/cells8121498
Publisher version: https://doi.org/10.3390/cells8121498
Language: English
Additional information: © 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/).
Keywords: Nova2; alternative splicing; angiogenesis; vascular development; post-transcriptional regulation
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10087702
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