TRMT1L-catalyzed m22G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress.

Hwang, S.-P.; Liao, H.; Barondeau, K.; Han, X.; Herbert, C.; McConnie, H.; Shekar, A.; Pestov, D.; Limbach, P. A.; Chang, J. T.; Denicourt, C.

doi:10.1101/2024.05.02.591343

bioRxiv · 10.1101/2024.05.02.591343

TRMT1L-catalyzed m22G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress.

Hwang, S.-P.·Liao, H.·Barondeau, K.·Han, X.·Herbert, C.·McConnie, H.·Shekar, A.·Pestov, D.·Limbach, P. A.·Chang, J. T.·Denicourt, C.

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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 m22G 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 oxidative stress. Our results establish TRMT1L as the elusive methyltransferase catalyzing the m22G27 modification on tRNA Tyr, resolving a long-standing gap of knowledge and highlighting its potential role in a tRNA modification circuit crucial for translation regulation and stress response.

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Hwang, S.-P., Liao, H., Barondeau, K., Han, X., Herbert, C., McConnie, H., Shekar, A., Pestov, D., Limbach, P. A., Chang, J. T., Denicourt, C.. 2024-05-03. TRMT1L-catalyzed m22G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress.. https://doi.org/10.1101/2024.05.02.591343

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