Mettl3-dependent m6A modification is essential for effector differentiation and memory formation of CD8+ T cells [SLIM-seq]

The goal of this study is to determine the critical requirement of N6-Methyladenosine (m6A) methyltransferase Mettl3 during CD8+ T cell responses upon acute viral infection. We demonstrate that conditional ablation of Mettl3 in CD8+ T cells impairs effector expansion and terminal differentiation in an m6A-dependent manner, which in turn affects memory formation and secondary response. Mechanism analysis indicates that Mettl3 deficiency broadly affects expression of cell cycle and transcriptional regulators. Based on these findings, our study reveals the important role of m6A modification in CD8+ T cell responses. Wild-type naïve (CD44-CD62L+) CD8+ T cells (3 samples per group), effector (CD44+CD62L-) CD8+ T cells (3 samples per group) and memory (CD44+CD62L+) CD8+ T cells (3 samples per group) were sorted