TRMT1L-catalyzed m² ₂G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress.

ABSTRACT: tRNA modifications are critical for several aspects of their functions, including decoding, folding, and stability. Using a multifaceted approach encompassing eCLIP-seq and Nanopore tRNA-seq, we show that the human tRNA methyltransferase TRMT1L interacts with component of the Rix1 ribosome biogenesis complex and binds to the 28S rRNA, as well as to a subset of tRNAs. Mechanistically, we demonstrate that TRMT1L is responsible for catalyzing m² ₂G solely at position 27 of tRNA-Tyr-GUA. Surprisingly, TRMT1L depletion also impaired the deposition of acp³U and dihydrouridine on tRNA-Tyr-GUA, Cys-GCA, and Ala-CGC. TRMT1L knockout cells have a marked decrease in tRNA-Tyr-GUA levels, coinciding with a reduction in global translation rates and hypersensitivity to ox

SUBMITTER: Hwang SP 

PROVIDER: S-EPMC11482778 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature