Structural insights into FTO's catalytic mechanism for the demethylation of multiple RNA substrates.

ABSTRACT: FTO demethylates internal N⁶-methyladenosine (m⁶A) and N⁶,2'-O-dimethyladenosine (m⁶A_m; at the cap +1 position) in mRNA, m⁶A and m⁶A_m in snRNA, and N¹-methyladenosine (m¹A) in tRNA in vivo, and in vitro evidence supports that it can also demethylate N⁶-methyldeoxyadenosine (6mA), 3-methylthymine (3mT), and 3-methyluracil (m³U). However, it remains unclear how FTO variously recognizes and catalyzes these diverse substrates. Here we demonstrate-in vitro and in vivo-that FTO has extensive demethylation enzymatic activity on both internal m⁶A and cap m⁶A_m Considering that 6mA, m⁶A, and

SUBMITTER: Zhang X 

PROVIDER: S-EPMC6386707 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature