TY - JOUR
T1 - N6-Methyladenosine Promotes TNF mRNA Degradation In CD4+ T Lymphocytes
AU - van Vroonhoven, Ellen C N
AU - Picavet, Lucas W
AU - Scholman, Rianne C
AU - Sijbers, Lyanne J P M
AU - Kievit, Corlinda R E
AU - van den Dungen, Noortje A M
AU - Mokry, Michal
AU - Evers, Anouk
AU - Lebbink, Robert J
AU - Mocholi, Enric
AU - Coffer, Paul J
AU - Calis, Jorg J A
AU - Vastert, Sebastiaan J
AU - van Loosdregt, Jorg
N1 - Publisher Copyright:
© 2024 The Author(s).
PY - 2024/10/1
Y1 - 2024/10/1
N2 - 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 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 messenger RNA (mRNA) after activation, predominantly in the 3' untranslated region 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 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.
AB - 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 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 messenger RNA (mRNA) after activation, predominantly in the 3' untranslated region 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 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.
U2 - 10.1093/jleuko/qiae087
DO - 10.1093/jleuko/qiae087
M3 - Article
C2 - 38657004
SN - 0741-5400
VL - 116
SP - 807
EP - 815
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 4
ER -