期刊
CELLS
卷 8, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/cells8121498
关键词
Nova2; alternative splicing; angiogenesis; vascular development; post-transcriptional regulation
类别
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG-17395]
- AIRC - FIRC ITALY postdoctoral fellowship
- Fondazione Adriano Buzzati-Traverso postdoctoral fellowship
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-gamma) and E2F1 transcription factors. We also showed that Nova2 in ECs controlled the AS profiles of Ppar-gamma and E2F dimerization partner 2 (Tfdp2), thus generating different protein isoforms with distinct function (Ppar-gamma) or subcellular localization (Tfdp2). Collectively, our results supported a mechanism whereby Nova2 integrated splicing decisions in order to regulate Ppar-gamma 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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