Kunze, Michael M. ; Benz, Fabienne ; Brauß, Thilo F. ; Lampe, Sebastian ; Weigand, Julia E. ; Braun, Johannes ; Richter, Florian M. ; Wittig, Ilka ; Brüne, Bernhard ; Schmid, Tobias (2016)
sST2 translation is regulated by FGF2 via an hnRNP A1-mediated IRES-dependent mechanism.
In: Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, 1859 (7)
doi: 10.1016/j.bbagrm.2016.05.005
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Translation is an energy-intensive process and tightly regulated. Generally, translation is initiated in a cap-dependent manner. Under stress conditions, typically found within the tumor microenvironment in association with e.g. nutrient deprivation or hypoxia, cap-dependent translation decreases, and alternative modes of translation initiation become more important. Specifically, internal ribosome entry sites (IRES) facilitate translation of specific mRNAs under otherwise translation-inhibitory conditions. This mechanism is controlled by IRES trans-acting factors (ITAF), i.e. by RNA-binding proteins, which interact with and determine the activity of selected IRESs. We aimed at characterizing the translational regulation of the IL-33 decoy receptor sST2, which was enhanced by fibroblast growth factor 2 (FGF2). We identified and verified an IRES within the 5'UTR of sST2. Furthermore, we found that MEK/ERK signaling contributes to FGF2-induced, sST2-IRES activation and translation. Determination of the sST2-5'UTR structure by in-line probing followed by deletion analyses identified 23 nucleotides within the sST2-5'UTR to be required for optimal IRES activity. Finally, we show that the RNA-binding protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds to the sST2-5'UTR, acts as an ITAF, and thus controls the activity of the sST2-IRES and consequently sST2 translation. Specifically, FGF2 enhances nuclear-cytoplasmic translocation of hnRNP A1, which requires intact MEK/ERK activity. In summary, we provide evidence that the sST2-5'UTR contains an IRES element, which is activated by a MEK/ERK-dependent increase in cytoplasmic localization of hnRNP A1 in response to FGF2, enhancing the translation of sST2.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2016 |
| Autor(en): | Kunze, Michael M. ; Benz, Fabienne ; Brauß, Thilo F. ; Lampe, Sebastian ; Weigand, Julia E. ; Braun, Johannes ; Richter, Florian M. ; Wittig, Ilka ; Brüne, Bernhard ; Schmid, Tobias |
| Art des Eintrags: | Bibliographie |
| Titel: | sST2 translation is regulated by FGF2 via an hnRNP A1-mediated IRES-dependent mechanism |
| Sprache: | Englisch |
| Publikationsjahr: | 8 Mai 2016 |
| Verlag: | Elsevier |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms |
| Jahrgang/Volume einer Zeitschrift: | 1859 |
| (Heft-)Nummer: | 7 |
| DOI: | 10.1016/j.bbagrm.2016.05.005 |
| URL / URN: | https://www.sciencedirect.com/science/article/pii/S187493991... |
| Kurzbeschreibung (Abstract): | Translation is an energy-intensive process and tightly regulated. Generally, translation is initiated in a cap-dependent manner. Under stress conditions, typically found within the tumor microenvironment in association with e.g. nutrient deprivation or hypoxia, cap-dependent translation decreases, and alternative modes of translation initiation become more important. Specifically, internal ribosome entry sites (IRES) facilitate translation of specific mRNAs under otherwise translation-inhibitory conditions. This mechanism is controlled by IRES trans-acting factors (ITAF), i.e. by RNA-binding proteins, which interact with and determine the activity of selected IRESs. We aimed at characterizing the translational regulation of the IL-33 decoy receptor sST2, which was enhanced by fibroblast growth factor 2 (FGF2). We identified and verified an IRES within the 5'UTR of sST2. Furthermore, we found that MEK/ERK signaling contributes to FGF2-induced, sST2-IRES activation and translation. Determination of the sST2-5'UTR structure by in-line probing followed by deletion analyses identified 23 nucleotides within the sST2-5'UTR to be required for optimal IRES activity. Finally, we show that the RNA-binding protein heterogeneous ribonucleoprotein A1 (hnRNP A1) binds to the sST2-5'UTR, acts as an ITAF, and thus controls the activity of the sST2-IRES and consequently sST2 translation. Specifically, FGF2 enhances nuclear-cytoplasmic translocation of hnRNP A1, which requires intact MEK/ERK activity. In summary, we provide evidence that the sST2-5'UTR contains an IRES element, which is activated by a MEK/ERK-dependent increase in cytoplasmic localization of hnRNP A1 in response to FGF2, enhancing the translation of sST2. |
| ID-Nummer: | pmid:27168114 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > RNA Biochemie |
| Hinterlegungsdatum: | 05 Mär 2021 07:36 |
| Letzte Änderung: | 05 Mär 2021 07:36 |
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