METTL3-mediated m⁶A RNA methylation promotes the anti-tumour immunity of natural killer cells.

ABSTRACT: Natural killer (NK) cells exert critical roles in anti-tumor immunity but how their functions are regulated by epitranscriptional modification (e.g., N⁶-methyladenosine (m⁶A) methylation) is unclear. Here we report decreased expression of the m⁶A "writer" METTL3 in tumor-infiltrating NK cells, and a positive correlation between protein expression levels of METTL3 and effector molecules in NK cells. Deletion of Mettl3 in NK cells alters the homeostasis of NK cells and inhibits NK cell infiltration and function in the tumor microenvironment, leading to accelerated tumor development and shortened survival in mice. The gene encoding SHP-2 is m⁶A modified, and its protein expression is decreased in METTL3-deficient NK cells. Reduced SHP-2 activity ren

SUBMITTER: Song H 

PROVIDER: S-EPMC8448775 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature