The m6A modification in regulating CD8 T cell response (IMAGE)
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During viral infection, total m6A levels in Naïve stage, effector stage, and memory stage exhibit dynamic alteration (high-low-high). The presence of Mettl3 promotes CD8 T cell expansion and terminal differentiation in an m6A-dependent manner, which in turn affects memory formation and secondary response. With m6A machinery, Mettl3 regulates CD8 T cell response via post-transcriptionally regulating genes involved in cell cycle (including Ccna2, Ccne2, Anapc7, and Mnat1), cell apoptosis (including Dad1, Tnf, and Tnfrsf9) and T cell differentiation (including Tbx21, Il7r, Id3, and Dtx1). In particular, Mettl3 binds Tbx21 transcript and sustains its stability, allowing normal production of T-bet protein, which in return boosts CD8 T cell effector differentiation.
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