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

N-methyladenine (mA), a modification of transcripts, regulates mRNA structure and translation efficiency. In a recent issue of Nature, Sun et al. reported that mA 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 mA. The study is especially important for revealing the pathological function of mA in RNA and the pathological mechanisms of CAG repeat expansion-related neurodegenerative diseases.