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Diabetologia
Published in: Diabetologia 7/2013

Open Access 01-07-2013 | Article

Co-regulation of intragenic microRNA miR-153 and its host gene Ia-2 β: identification of miR-153 target genes with functions related to IA-2β in pancreas and brain

Authors: W. Mandemakers, L. Abuhatzira, H. Xu, L. A. Caromile, S. S. Hébert, A. Snellinx, V. A. Morais, S. Matta, T. Cai, A. L. Notkins, B. De Strooper

Published in: Diabetologia | Issue 7/2013

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Abstract

Aims/hypothesis

We analysed the genomic organisation of miR-153, a microRNA embedded in genes that encode two of the major type 1 diabetes autoantigens, islet-associated protein (IA)-2 and IA-2β. We also identified miR-153 target genes that correlated with IA-2β localisation and function.

Methods

A bioinformatics approach was used to identify miR-153’s genomic organisation. To analyse the co-regulation of miR-153 and IA-2β, quantitative PCR analysis of miR-153 and Ia-2β (also known as Ptprn2) was performed after a glucose stimulation assay in MIN6B cells and isolated murine pancreatic islets, and also in wild-type Ia-2 (also known as Ptprn), Ia-2β single knockout and Ia-2/Ia-2β double knockout mouse brain and pancreatic islets. Bioinformatics identification of miR-153 target genes and validation via luciferase reporter assays, western blotting and quantitative PCR were also carried out.

Results

Two copies of miR-153, miR-153-1 and miR-153-2, are localised in intron 19 of Ia-2 and Ia-2β, respectively. In rodents, only miR-153-2 is conserved. We demonstrated that expression of miR-153-2 and Ia-2β in rodents is partially co-regulated as demonstrated by a strong reduction of miR-153 expression levels in Ia-2β knockout and Ia-2/Ia-2β double knockout mice. miR-153 levels were unaffected in Ia-2 knockout mice. In addition, glucose stimulation, which increases Ia-2 and Ia-2β expression, also significantly increased expression of miR-153. Several predicted targets of miR-153 were reduced after glucose stimulation in vitro, correlating with the increase in miR-153 levels.

Conclusions/interpretation

This study suggests the involvement of miR-153, IA-2β and miR-153 target genes in a regulatory network, which is potentially relevant to insulin and neurotransmitter release.
Appendix
Available only for authorised users
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Metadata
Title
Co-regulation of intragenic microRNA miR-153 and its host gene Ia-2 β: identification of miR-153 target genes with functions related to IA-2β in pancreas and brain
Authors
W. Mandemakers
L. Abuhatzira
H. Xu
L. A. Caromile
S. S. Hébert
A. Snellinx
V. A. Morais
S. Matta
T. Cai
A. L. Notkins
B. De Strooper
Publication date
01-07-2013
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 7/2013
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-013-2901-5

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