Molecular Biology Reports

, Volume 39, Issue 7, pp 7813–7822 | Cite as

Induction and activation of antiviral enzyme 2′,5′-oligoadenylate synthetase by in vitro transcribed insulin mRNA and other cellular RNAs

  • Meixia Dan
  • Dongjun Zheng
  • L. Leigh Field
  • Vagn Bonnevie-Nielsen


Double-stranded RNA (dsRNA) can induce antiviral enzyme 2′,5′-oligoadenylate synthetase (2′5′AS) expression and activate latent 2′5′AS. Our previous data have shown pancreatic β cells are sensitive to dsRNA-induced 2′5′AS expression, and constitutive high basal 2′5′AS expression is associated with susceptibility to developing type 1 diabetes (T1D), a disease due to pancreatic β cell loss. Here we report that in vitro transcribed human insulin mRNA induces the activation of human OAS gene promoter sequences, and specifically and dose-dependently induces 2′5′AS expression in murine pancreatic βTC3 cells. Over-expression of dsRNA receptor retinoic acid-inducible gene-1 enhances insulin mRNA-induced 2′5′AS expression. In vitro transcribed insulin and other mRNAs, as well as total cellular RNAs, activate latent 2′5′AS in vitro with activation ability likely associated with the sequence and length of individual mRNAs or the sample source of total cellular RNA. Insulin mRNA does not show any specificity to activate 2′5′AS, but total cellular RNA from βTC3 cells has high activation ability. Constitutive 2′5′AS expression in βTC3 cells leads to cell proliferation inhibition and apoptosis. Our study suggests the possibility of cellular RNA-regulated 2′5′AS expression and activation, and the potential risk of high insulin gene transcription in pancreatic β cells, and may help explain genetic predisposition to T1D associated with INS VNTR class I alleles.


2′,5′-Oligoadenylate synthetase Double-stranded RNA Pancreatic beta cell INS VNTR 



2′,5′-Oligoadenylate synthetase


Double-stranded RNA



This research was funded by the Danish Health Science Research Council, the Danish Diabetes Association, NovoNordisk Foundation, Denmark, and the Juvenile Diabetes Research Foundation International.


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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Meixia Dan
    • 1
  • Dongjun Zheng
    • 1
  • L. Leigh Field
    • 2
  • Vagn Bonnevie-Nielsen
    • 1
  1. 1.Department of Pathology and Laboratory MedicineUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Medical GeneticsUniversity of British ColumbiaVancouverCanada

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