PMID- 25249621
OWN - NLM
STAT- MEDLINE
DCOM- 20150115
LR  - 20221207
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 42
IP  - 18
DP  - 2014 Oct
TI  - Nova1 is a master regulator of alternative splicing in pancreatic beta cells.
PG  - 11818-30
LID - 10.1093/nar/gku861 [doi]
AB  - 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.
CI  - (c) The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Villate, Olatz
AU  - Villate O
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium deizirik@ulb.ac.be.
FAU - Turatsinze, Jean-Valery
AU  - Turatsinze JV
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium.
FAU - Mascali, Loriana G
AU  - Mascali LG
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium.
FAU - Grieco, Fabio A
AU  - Grieco FA
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium.
FAU - Nogueira, Tatiane C
AU  - Nogueira TC
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium.
FAU - Cunha, Daniel A
AU  - Cunha DA
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium.
FAU - Nardelli, Tarlliza R
AU  - Nardelli TR
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium.
FAU - Sammeth, Michael
AU  - Sammeth M
AD  - Laboratorio Nacional de Computacao Cientifica (LNCC), Petropolis Rio de Janeiro, 
      25651-076, Brazil.
FAU - Salunkhe, Vishal A
AU  - Salunkhe VA
AD  - Lund University Diabetes Centre, Unit of Islet cell Exocytosis, Department of 
      Clinical Sciences Malmo, Lund University, CRC 91-11, Jan Waldenstroms gata 35, 
      205 02 Malmo, Sweden.
FAU - Esguerra, Jonathan L S
AU  - Esguerra JL
AD  - Lund University Diabetes Centre, Unit of Islet cell Exocytosis, Department of 
      Clinical Sciences Malmo, Lund University, CRC 91-11, Jan Waldenstroms gata 35, 
      205 02 Malmo, Sweden.
FAU - Eliasson, Lena
AU  - Eliasson L
AD  - Lund University Diabetes Centre, Unit of Islet cell Exocytosis, Department of 
      Clinical Sciences Malmo, Lund University, CRC 91-11, Jan Waldenstroms gata 35, 
      205 02 Malmo, Sweden.
FAU - Marselli, Lorella
AU  - Marselli L
AD  - Department of Clinical and Experimental Medicine, Pancreatic Islet Cell 
      Laboratory, University of Pisa, Pisa, 56126, Italy.
FAU - Marchetti, Piero
AU  - Marchetti P
AD  - Department of Clinical and Experimental Medicine, Pancreatic Islet Cell 
      Laboratory, University of Pisa, Pisa, 56126, Italy.
FAU - Eizirik, Decio L
AU  - Eizirik DL
AD  - ULB Center for Diabetes Research, Medical Faculty, Universite Libre de Bruxelles, 
      Brussels (ULB) B-1070, Belgium deizirik@ulb.ac.be.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140923
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Cytokines)
RN  - 0 (FOXO3 protein, rat)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Insulin)
RN  - 0 (NOVA1 protein, human)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuro-Oncological Ventral Antigen)
RN  - 0 (Nova1 protein, rat)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Foxo1 protein, rat)
RN  - EC 2.7.10.1 (Receptor, Insulin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - *Alternative Splicing
MH  - Animals
MH  - Apoptosis
MH  - Calcium/metabolism
MH  - Cytokines/pharmacology
MH  - Forkhead Box Protein O3
MH  - Forkhead Transcription Factors/metabolism
MH  - Gene Expression Profiling
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin-Secreting Cells/*metabolism
MH  - Nerve Tissue Proteins/metabolism
MH  - Neuro-Oncological Ventral Antigen
MH  - RNA-Binding Proteins/antagonists & inhibitors/genetics/*physiology
MH  - Rats, Wistar
MH  - Receptor, Insulin/genetics/metabolism
PMC - PMC4191425
EDAT- 2014/09/25 06:00
MHDA- 2015/01/16 06:00
PMCR- 2014/09/23
CRDT- 2014/09/25 06:00
PHST- 2014/09/25 06:00 [entrez]
PHST- 2014/09/25 06:00 [pubmed]
PHST- 2015/01/16 06:00 [medline]
PHST- 2014/09/23 00:00 [pmc-release]
AID - gku861 [pii]
AID - 10.1093/nar/gku861 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2014 Oct;42(18):11818-30. doi: 10.1093/nar/gku861. Epub 2014 
      Sep 23.