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Nova1 is a master regulator of alternative splicing in pancreatic beta cells.

Villate, Olatz; Turatsinze, Jean-Valery; Mascali, Loriana G; Grieco, Fabio A; Nogueira, Tatiane C; Cunha, Daniel A; Nardelli, Tarlliza R; Sammeth, Michael; Salunkhe, Vishal Ashok LU and Esguerra, Jonathan LU , et al. (2014) In Nucleic Acids Research 42(18). p.11818-11830
Abstract
Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the 'neuron-specific' Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signaling, splicing and transcription. In line with... (More)
Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the 'neuron-specific' Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signaling, splicing and transcription. In line with these findings, Nova1 silencing inhibited insulin secretion and induced apoptosis basally and after cytokine treatment in rodent and human beta cells. These observations identify a novel layer of regulation of beta cell function, namely AS controlled by key splicing regulators such as Nova1. (Less)
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publication status
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Nucleic Acids Research
volume
42
issue
18
pages
11818 - 11830
publisher
Oxford University Press
external identifiers
  • pmid:25249621
  • wos:000347687100051
  • scopus:84922367943
ISSN
1362-4962
DOI
10.1093/nar/gku861
language
English
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yes
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ae09aad3-dc14-49b4-898e-e9f6f1423d97 (old id 4690999)
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http://www.ncbi.nlm.nih.gov/pubmed/25249621?dopt=Abstract
date added to LUP
2014-10-08 15:56:02
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2017-11-12 03:15:45
@article{ae09aad3-dc14-49b4-898e-e9f6f1423d97,
  abstract     = {Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the 'neuron-specific' Nova1 splicing factor is expressed in pancreatic beta cells. We have presently coupled specific knockdown (KD) of Nova1 with RNA-sequencing to determine all splice variants and downstream pathways regulated by this protein in beta cells. Nova1 KD altered the splicing of nearly 5000 transcripts. Pathway analysis indicated that these genes are involved in exocytosis, apoptosis, insulin receptor signaling, splicing and transcription. In line with these findings, Nova1 silencing inhibited insulin secretion and induced apoptosis basally and after cytokine treatment in rodent and human beta cells. These observations identify a novel layer of regulation of beta cell function, namely AS controlled by key splicing regulators such as Nova1.},
  author       = {Villate, Olatz and Turatsinze, Jean-Valery and Mascali, Loriana G and Grieco, Fabio A and Nogueira, Tatiane C and Cunha, Daniel A and Nardelli, Tarlliza R and Sammeth, Michael and Salunkhe, Vishal Ashok and Esguerra, Jonathan and Eliasson, Lena and Marselli, Lorella and Marchetti, Piero and Eizirik, Decio L},
  issn         = {1362-4962},
  language     = {eng},
  number       = {18},
  pages        = {11818--11830},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {Nova1 is a master regulator of alternative splicing in pancreatic beta cells.},
  url          = {http://dx.doi.org/10.1093/nar/gku861},
  volume       = {42},
  year         = {2014},
}