METTL3 inhibition for FUS-mutant ALS

Inhibiting METTL3, a which adds N(6)-methyladenosine (m6A) modifications onto RNA, could help treat ALS caused by FUS mutations by reducing the formation of FUS-containing stress granules, which are cytoplasmic ribonucleoprotein assemblies that drive disease.

In a human neuroblastoma cell line engineered to express mutant FUS and exposed to stress granule-inducing stimuli, METTL3 shRNA knockdown and the resulting global decrease in m6A marks on RNA altered the RNA content in mutant-FUS containing stress granules to resemble that of similarly stimulated cells expressing a wildtype FUS transgene...