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ludc web

Lena Eliasson

Principal investigator

ludc web

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

Author

  • Olatz Villate
  • Jean-Valery Turatsinze
  • Loriana G Mascali
  • Fabio A Grieco
  • Tatiane C Nogueira
  • Daniel A Cunha
  • Tarlliza R Nardelli
  • Michael Sammeth
  • Vishal Ashok Salunkhe
  • Jonathan Esguerra
  • Lena Eliasson
  • Lorella Marselli
  • Piero Marchetti
  • Decio L Eizirik

Summary, in English

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.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2014

Language

English

Pages

11818-11830

Publication/Series

Nucleic Acids Research

Volume

42

Issue

18

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 1362-4962