Syntaxin-1a is a direct target of miR-29a in insulin-producing beta-cells

Annika Bagge, Christina Mackeprang Dahmcke, Louise Torp Dalgaard

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    Downregulation of proteins involved in the ­exocytotic machinery has been implicated in the impairment of normal β-cell function in response to high glucose levels. Syntaxin-1a ­(Stx-1a) is one of two t-SNAREs involved in insulin exocytosis and decreased expression of Stx-1a protein impairs glucose-stimulated insulin secretion (GSIS) in isolated rat pancreatic islets. In diabetic patients Stx-1a protein levels are reduced, but the mechanism of this suppression is unknown.

    MicroRNAs are small noncoding RNAs, which are important regulators of gene-expression at the post transcriptional level, partially binding to the 3′UTRs of their target gene transcripts either mediating transcript degradation or inhibiting translation. We have recently shown that miR-29a is upregulated in response to elevated glucose levels in β-cells and is involved in mediating the negative effect of high glucose levels on GSIS. Stx-1a has a predicted target site of miR-29a present in its 3′ untranslated region. The objective of this study was to evaluate whether miR-29a targets Stx-1a directly to decrease mRNA and/or protein levels in response to glucose. Stx-1a mRNA and protein levels decreased in β-cells treated with increased glucose levels. Overexpression of miR-29a decreased Stx-1a mRNA and protein levels. Furthermore, miR-29a decreases the response of a luciferase reporter construct containing the predicted target site normally present in the Stx-1a gene. When 2 nucleotides are mutated in this target site, responsiveness to miR-29a disappears, confirming miR-29a binding to this sequence. Collectively, these data implicate miR-29a as a mediator of glucose-induced downregulation of Stx-1a in β-cells.
    OriginalsprogEngelsk
    TidsskriftHormone and Metabolic Research
    Vol/bind45
    Udgave nummer6
    Sider (fra-til)463-466
    ISSN0018-5043
    DOI
    StatusUdgivet - 11 jan. 2013

    Citer dette

    Bagge, Annika ; Dahmcke, Christina Mackeprang ; Dalgaard, Louise Torp. / Syntaxin-1a is a direct target of miR-29a in insulin-producing beta-cells. I: Hormone and Metabolic Research. 2013 ; Bind 45, Nr. 6. s. 463-466.
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    title = "Syntaxin-1a is a direct target of miR-29a in insulin-producing beta-cells",
    abstract = "Downregulation of proteins involved in the ­exocytotic machinery has been implicated in the impairment of normal β-cell function in response to high glucose levels. Syntaxin-1a ­(Stx-1a) is one of two t-SNAREs involved in insulin exocytosis and decreased expression of Stx-1a protein impairs glucose-stimulated insulin secretion (GSIS) in isolated rat pancreatic islets. In diabetic patients Stx-1a protein levels are reduced, but the mechanism of this suppression is unknown.MicroRNAs are small noncoding RNAs, which are important regulators of gene-expression at the post transcriptional level, partially binding to the 3′UTRs of their target gene transcripts either mediating transcript degradation or inhibiting translation. We have recently shown that miR-29a is upregulated in response to elevated glucose levels in β-cells and is involved in mediating the negative effect of high glucose levels on GSIS. Stx-1a has a predicted target site of miR-29a present in its 3′ untranslated region. The objective of this study was to evaluate whether miR-29a targets Stx-1a directly to decrease mRNA and/or protein levels in response to glucose. Stx-1a mRNA and protein levels decreased in β-cells treated with increased glucose levels. Overexpression of miR-29a decreased Stx-1a mRNA and protein levels. Furthermore, miR-29a decreases the response of a luciferase reporter construct containing the predicted target site normally present in the Stx-1a gene. When 2 nucleotides are mutated in this target site, responsiveness to miR-29a disappears, confirming miR-29a binding to this sequence. Collectively, these data implicate miR-29a as a mediator of glucose-induced downregulation of Stx-1a in β-cells.",
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    Syntaxin-1a is a direct target of miR-29a in insulin-producing beta-cells. / Bagge, Annika; Dahmcke, Christina Mackeprang; Dalgaard, Louise Torp.

    I: Hormone and Metabolic Research, Bind 45, Nr. 6, 11.01.2013, s. 463-466.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Syntaxin-1a is a direct target of miR-29a in insulin-producing beta-cells

    AU - Bagge, Annika

    AU - Dahmcke, Christina Mackeprang

    AU - Dalgaard, Louise Torp

    PY - 2013/1/11

    Y1 - 2013/1/11

    N2 - Downregulation of proteins involved in the ­exocytotic machinery has been implicated in the impairment of normal β-cell function in response to high glucose levels. Syntaxin-1a ­(Stx-1a) is one of two t-SNAREs involved in insulin exocytosis and decreased expression of Stx-1a protein impairs glucose-stimulated insulin secretion (GSIS) in isolated rat pancreatic islets. In diabetic patients Stx-1a protein levels are reduced, but the mechanism of this suppression is unknown.MicroRNAs are small noncoding RNAs, which are important regulators of gene-expression at the post transcriptional level, partially binding to the 3′UTRs of their target gene transcripts either mediating transcript degradation or inhibiting translation. We have recently shown that miR-29a is upregulated in response to elevated glucose levels in β-cells and is involved in mediating the negative effect of high glucose levels on GSIS. Stx-1a has a predicted target site of miR-29a present in its 3′ untranslated region. The objective of this study was to evaluate whether miR-29a targets Stx-1a directly to decrease mRNA and/or protein levels in response to glucose. Stx-1a mRNA and protein levels decreased in β-cells treated with increased glucose levels. Overexpression of miR-29a decreased Stx-1a mRNA and protein levels. Furthermore, miR-29a decreases the response of a luciferase reporter construct containing the predicted target site normally present in the Stx-1a gene. When 2 nucleotides are mutated in this target site, responsiveness to miR-29a disappears, confirming miR-29a binding to this sequence. Collectively, these data implicate miR-29a as a mediator of glucose-induced downregulation of Stx-1a in β-cells.

    AB - Downregulation of proteins involved in the ­exocytotic machinery has been implicated in the impairment of normal β-cell function in response to high glucose levels. Syntaxin-1a ­(Stx-1a) is one of two t-SNAREs involved in insulin exocytosis and decreased expression of Stx-1a protein impairs glucose-stimulated insulin secretion (GSIS) in isolated rat pancreatic islets. In diabetic patients Stx-1a protein levels are reduced, but the mechanism of this suppression is unknown.MicroRNAs are small noncoding RNAs, which are important regulators of gene-expression at the post transcriptional level, partially binding to the 3′UTRs of their target gene transcripts either mediating transcript degradation or inhibiting translation. We have recently shown that miR-29a is upregulated in response to elevated glucose levels in β-cells and is involved in mediating the negative effect of high glucose levels on GSIS. Stx-1a has a predicted target site of miR-29a present in its 3′ untranslated region. The objective of this study was to evaluate whether miR-29a targets Stx-1a directly to decrease mRNA and/or protein levels in response to glucose. Stx-1a mRNA and protein levels decreased in β-cells treated with increased glucose levels. Overexpression of miR-29a decreased Stx-1a mRNA and protein levels. Furthermore, miR-29a decreases the response of a luciferase reporter construct containing the predicted target site normally present in the Stx-1a gene. When 2 nucleotides are mutated in this target site, responsiveness to miR-29a disappears, confirming miR-29a binding to this sequence. Collectively, these data implicate miR-29a as a mediator of glucose-induced downregulation of Stx-1a in β-cells.

    U2 - 10.1055/s-0032-1333238

    DO - 10.1055/s-0032-1333238

    M3 - Journal article

    VL - 45

    SP - 463

    EP - 466

    JO - Hormone and Metabolic Research

    JF - Hormone and Metabolic Research

    SN - 0018-5043

    IS - 6

    ER -