A new role for PHYHD1 and related dioxygenases: demethylation of 2'-O-methylated nucleosides.

ABSTRACT: Nucleoside 2'-O-methylation is a widespread RNA modification found across diverse RNA types in all domains of life. Although considerable progress has been made in mapping 2'-O-methylation sites and elucidating their biological roles, the enzymatic pathways responsible for the catabolism of 2'-O-methylated nucleosides remain largely unexplored. Here, we report a previously unidentified 2'-O-methylated nucleoside demethylation reaction catalyzed by a metagenome-derived bacterial dioxygenase named FJS. We further show that FJS-related enzymes, including human phytanoyl-CoA dioxygenase domain-containing protein 1 (PHYHD1), catalyze the 2-oxoglutarate-dependent demethylation of a broad range of ribose-methylated nucleosides, but do not act on modified nucleotides or 3'-terminal 2'-O-methylated

SUBMITTER: Stonkus J 

PROVIDER: S-EPMC12709175 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature