CAG Repeat Expansions Increase N(1)-Methyladenine to Alter TDP-43 Phase Separation: Lights Up Therapeutic Intervention for Neurodegeneration

N(1)-methyladenine (m(1)A), a modification of transcripts, regulates mRNA structure and translation efficiency. In a recent issue of Nature, Sun et al. reported that m(1)A in CAG repeat RNA contributes to CAG repeat expansion-induced neurodegeneration in Caenorhabditis elegans and Drosophila through enhancing the ability of endogenous TDP-43 to partition into stress granules mediated by m(1)A. The study is especially important for revealing the pathological function of m(1)A in RNA and the pathological mechanisms of CAG repeat expansion-related neurodegenerative diseases.