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- W4362664462 abstract "How N6-methyladenosine (m6A), the most abundant mRNA modification, contributes to primate tissue homeostasis and physiological aging remains elusive. Here, we characterize the m6A epitranscriptome across the liver, heart and skeletal muscle in young and old nonhuman primates. Our data reveal a positive correlation between m6A modifications and gene expression homeostasis across tissues as well as tissue-type-specific aging-associated m6A dynamics. Among these tissues, skeletal muscle is the most susceptible to m6A loss in aging and shows a reduction in the m6A methyltransferase METTL3. We further show that METTL3 deficiency in human pluripotent stem cell-derived myotubes leads to senescence and apoptosis, and identify NPNT as a key element downstream of METTL3 involved in myotube homeostasis, whose expression and m6A levels are both decreased in senescent myotubes. Our study provides a resource for elucidating m6A-mediated mechanisms of tissue aging and reveals a METTL3–m6A–NPNT axis counteracting aging-associated skeletal muscle degeneration. The authors characterized m6A dynamics in primate tissue aging and revealed a new role for the METTL3–m6A–NPNT axis in maintaining skeletal muscle homeostasis, thereby providing insight into the epitranscriptomic machinery underlying primate aging." @default.
- W4362664462 created "2023-04-07" @default.
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- W4362664462 date "2023-04-06" @default.
- W4362664462 modified "2023-10-17" @default.
- W4362664462 title "m6A epitranscriptomic regulation of tissue homeostasis during primate aging" @default.
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