Intellectual disability-associated gene ftsj1 is responsible for 2'-O-methylation of specific tRNAs.

ABSTRACT: tRNA modifications at the anti-codon loop are critical for accurate decoding. FTSJ1 was hypothesized to be a human tRNA 2'-O-methyltransferase. tRNA^Phe (GAA) from intellectual disability patients with mutations in ftsj1 lacks 2'-O-methylation at C32 and G34 (Cm32 and Gm34). However, the catalytic activity, RNA substrates, and pathogenic mechanism of FTSJ1 remain unknown, owing, in part, to the difficulty in reconstituting enzymatic activity in vitro. Here, we identify an interacting protein of FTSJ1, WDR6. For the first time, we reconstitute the 2'-O-methylation activity of the FTSJ1-WDR6 complex in vitro, which occurs at position 34 of specific tRNAs with m¹ G37 as a prerequisite. We find that modifications at positions 32, 34, and 37 are interdependent and occur in

SUBMITTER: Li J 

PROVIDER: S-EPMC7403668 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature