FTO controls reversible m⁶Am RNA methylation during snRNA biogenesis.

ABSTRACT: Small nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA splicing. Here we show that snRNAs contain a regulated and reversible nucleotide modification causing them to exist as two different methyl isoforms, m₁ and m₂, reflecting the methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA biogenesis involves the formation of an initial m₁ isoform with a single-methylated adenosine (2'-O-methyladenosine, Am), which is then converted to a dimethylated m₂ isoform (N⁶,2'-O-dimethyladenosine, m⁶Am). The relative m₁ and m₂ isoform levels are determined by the RNA demethylase FTO, which selectively demethylates the m₂ isoform. We show FTO is inhibited

SUBMITTER: Mauer J 

PROVIDER: S-EPMC6984009 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature