Nova1 is a Master Regulator of Alternative Splicing in Pancreatic Beta Cells

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2014 Sep 25

PMID 25249621

Citations 56

Authors

Olatz Villate

Jean-Valery Turatsinze

Loriana G Mascali

Fabio A Grieco

Tatiane C Nogueira

Daniel A Cunha

Tarlliza R Nardelli

Michael Sammeth

Vishal A Salunkhe

Jonathan L S Esguerra

Lena Eliasson

Lorella Marselli

Piero Marchetti

Decio L Eizirik

Affiliations

Soon will be listed here.

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.

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