دورية أكاديمية
N6-Methyladenosine Promotes TNF mRNA Degradation In CD4+ T Lymphocytes.
| العنوان: | N6-Methyladenosine Promotes TNF mRNA Degradation In CD4+ T Lymphocytes. |
|---|---|
| المؤلفون: | van Vroonhoven ECN; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., Picavet LW; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., Scholman RC; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., Sijbers LJPM; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., Kievit CRE; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., van den Dungen NAM; Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands., Mokry M; Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands., Evers A; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands., Lebbink RJ; Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands., Mocholi E; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands., Coffer PJ; Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.; Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, the Netherlands., Calis JJA; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., Vastert SJ; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Pediatric Rheumatology and Immunology, University Medical Center Utrecht, Utrecht, the Netherlands., van Loosdregt J; Center for Translational Immunology, University Medical Center Utrecht, Utrecht, the Netherlands. |
| المصدر: | Journal of leukocyte biology [J Leukoc Biol] 2024 Apr 24. Date of Electronic Publication: 2024 Apr 24. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 8405628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1938-3673 (Electronic) Linking ISSN: 07415400 NLM ISO Abbreviation: J Leukoc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2023- : Oxford : Oxford University Press Original Publication: New York : Alan R. Liss, c1984- |
| مستخلص: | N6-methyladenosine (m6A) is a RNA modification that can regulate post-transcriptional processes including RNA stability, translation, splicing and nuclear export. In CD4+ lymphocytes, m6A modifications have been demonstrated to play a role in early differentiation processes. The role of m6A in CD4+ T cell activation and effector function remains incompletely understood. To assess the role of m6A in CD4+ T lymphocyte activation and function, we assessed the transcriptome-wide m6A landscape of human primary CD4+ T cells by methylated RNA immunoprecipitation (meRIP) sequencing. Stimulation of the T cells impacted the m6A pattern of hundreds of transcripts including tumor necrosis factor (TNF). m6A methylation was increased on TNF mRNA after activation, predominantly in the 3' untranslated region (UTR) of the transcript. Manipulation of m6A levels in primary human T cells, the directly affected the expression of TNF. Furthermore, we identified that the m6A reader protein YT521-B homology domain family-2 (YTHDF2) binds m6A-methylated TNF mRNA, and promotes its degradation. Taken together, this study demonstrates that TNF expression in CD4+ T lymphocytes is regulated via m6A and YTHDF2, thereby providing novel insight into the regulation of T cell effector functions. (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.) |
| فهرسة مساهمة: | Keywords: RNA methylation; T cell activation; Tumor Necrosis Factor; adaptive immunity; epitranscriptomics Local Abstract: [plain-language-summary] T helper cells are immune cells of the adaptive immune system. These cells are activated by antigen presenting cells that have engulfed invading pathogens. When the T helper cell is activated, it will produce and excrete signaling molecules (cytokines) that activate other immune cells in order to eradicate these pathogens. Cytokines are formed after translation of RNA molecules that encode for these cytokines. In this study it was found that a modification (m6A) on RNA molecules is involved in the regulation of the life cycle of these RNA molecules. It was found that the degradation of RNA encoding for cytokine TNF was mediated through m6A and its ‘reader’ protein YTHDF2 in activated T helper cells. As TNF promotes inflammation, reduction of TNF production through this mechanism dampens the immune response and therefore prevents chronic inflammation. |
| تواريخ الأحداث: | Date Created: 20240424 Latest Revision: 20240424 |
| رمز التحديث: | 20240425 |
| DOI: | 10.1093/jleuko/qiae087 |
| PMID: | 38657004 |
| قاعدة البيانات: | MEDLINE |
كن أول من يترك تعليقا!