Data from mTOR Signaling Promotes Rapid m⁶A mRNA Methylation to Regulate NK-Cell Activation and Effector Functions

• DOI: 10.1158/2326-6066.c.7380107.v1
• Publication Date: 2024-08-01T11:58:31Z
• Authors: Meng Meng; Zhaoyang Zhong; Liang Song; Zhaohui Zhang; Xiaofeng Yin; Xiqiang Xie; Lei Tian; Wei Wu; Yao Yang; Yafei Deng; Hongyan Peng; Shuting Wu; Guanghe Ran; Yuqing Lin; Qiangqiang Lai; Qinghua Bi; Fulin Yan; Yan Ji; Yang Wang; Xiaohui Li; Ping Yi; Jianhua Yu; Youcai Deng

<div>Abstract<p>NK cells can be rapidly activated in response to cytokines during host defense against malignant or viral infection. However, it remains unclear what mechanisms precisely and regulate the expression of a large number genes involved activating NK cells. In this study, we discovered that NK-cell <i>N</i><sup>6</sup>-methyladenosine (m<sup>6</sup>A) methylation levels were upregulated upon short-term activation repressed tumor microenvironment (TME). Deficiency methyltransferase-like 3 (METTL3) METTL14 moderately influenced homeostasis, while double-knockout METTL3/14 more significantly impacted maturation, antitumor immunity. This suggests cooperative role METTL3 regulating development effector functions. Using methylated RNA immunoprecipitation sequencing, demonstrated functions, such as <i>Prf1</i> <i>Gzmb</i>, directly modified by m<sup>6</sup>A methylation. Furthermore, inhibiting mTOR complex 1 prevented from increasing when activated, could restored S-adenosylmethionine supplementation. Collectively, have unraveled crucial roles for rapid mRNA downstream 1–S-adenosylmethionine signal axis functions.</p></div>