Academic Journal
Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes
| العنوان: | Assessment of mTOR-Dependent Translational Regulation of Interferon Stimulated Genes |
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| المؤلفون: | Livingstone, Mark, Sikström, Kristina, Robert, Philippe, Uzé, Gilles, Larsson, Ola, Pellegrini, Sandra |
| المساهمون: | Signalisation des Cytokines, Institut Pasteur Paris (IP)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet Stockholm, Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), This research was supported by funding (to ML) from the Pasteur Foundation, institutional support from Institut Pasteur and CNRS, and grants from the Swedish Research Council and the Wallenberg Academy Fellows program (to OL). |
| المصدر: | ISSN: 1932-6203. |
| بيانات النشر: | HAL CCSD Public Library of Science |
| سنة النشر: | 2015 |
| المجموعة: | Université de Montpellier: HAL |
| مصطلحات موضوعية: | MESH: Cell Line, MESH: Gene Expression Regulation, MESH: Humans, MESH: Interferon-beta, MESH: Naphthyridines, MESH: Phosphorylation, MESH: Protein Biosynthesis, MESH: TOR Serine-Threonine Kinases, [SDV.IMM]Life Sciences [q-bio]/Immunology |
| الوصف: | International audience ; Type-I interferon (IFN)-induced activation of the mammalian target of rapamycin (mTOR) signaling pathway has been implicated in translational control of mRNAs encoding inter-feron-stimulated genes (ISGs). However, mTOR-sensitive translatomes commonly include mRNAs with a 5' terminal oligopyrimidine tract (TOP), such as those encoding ribosomal proteins, but not ISGs. Because these translatomes were obtained under conditions when ISG expression is not induced, we examined the mTOR-sensitive translatome in human WISH cells stimulated with IFN β. The mTOR inhibitor Torin1 resulted in a repression of global protein synthesis, including that of ISG products, and translation of all but 3 ISG mRNAs (TLR3, NT5C3A, and RNF19B) was not selectively more sensitive to mTOR inhibition. Detailed studies of NT5C3A revealed an IFN-induced change in transcription start site resulting in a switch from a non-TOP to a TOP-like transcript variant and mTOR sensitive translation. Thus, we show that, in the cell model used, translation of the vast majority of ISG mRNAs is not selectively sensitive to mTOR activity and describe an uncharacterized mechanism wherein the 5'-UTR of an mRNA is altered in response to a cytokine, resulting in a shift from mTOR-insensitive to mTOR-sensitive translation. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/26207988; pasteur-02136942; https://hal-pasteur.archives-ouvertes.fr/pasteur-02136942; https://hal-pasteur.archives-ouvertes.fr/pasteur-02136942/document; https://hal-pasteur.archives-ouvertes.fr/pasteur-02136942/file/journal.pone.0133482%281%29.PDF; PUBMED: 26207988 |
| DOI: | 10.1371/journal.pone.0133482 |
| الاتاحة: | https://hal-pasteur.archives-ouvertes.fr/pasteur-02136942 https://hal-pasteur.archives-ouvertes.fr/pasteur-02136942/document https://hal-pasteur.archives-ouvertes.fr/pasteur-02136942/file/journal.pone.0133482%281%29.PDF https://doi.org/10.1371/journal.pone.0133482 |
| Rights: | http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.F4292858 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pone.0133482 |
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