M¹A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration.

ABSTRACT: Microsatellite repeat expansions within genes contribute to a number of neurological diseases^1,2. The accumulation of toxic proteins and RNA molecules with repetitive sequences, and/or sequestration of RNA-binding proteins by RNA molecules containing expanded repeats are thought to be important contributors to disease aetiology^3-9. Here we reveal that the adenosine in CAG repeat RNA can be methylated to N¹-methyladenosine (m¹A) by TRMT61A, and that m¹A can be demethylated by ALKBH3. We also observed that the m¹A/adenosine ratio in CAG repeat RNA increases with repeat length, which is attributed to diminished expression of ALKBH3 elicited by the repeat RNA. Additionally, TDP-43 binds directly and strongly with m¹A

SUBMITTER: Sun Y 

PROVIDER: S-EPMC10651481 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature