In C9ORF72-ALS/FTD, the hypomethylation of the repeat-containing intronic RNA (Extended Data Fig. 7a,9a) and the reduction of YTHDC1 protein (Extended Data Fig. 9b,c) could synergistically decelerate the RNA degradation, contributing to the increased accumulation of repeat RNA and DPRs with various toxicity. The gene discussed is YTHDC1; the disease is amyotrophic lateral sclerosis.