Poster abstracts

Poster number 163 submitted by Jiaming Mao

TRMT1 affects mitochondria function

Jiaming Mao (University of Rochester Biology ), Chenghong Deng (University of Rochester Biology ), Helen Jackson (University of Rochester Biology ), Naiyareen Mayeen (University of Rochester Biology ), Dr Kejia Zhang (University of Rochester Biology ), Dr Dragony Fu (University of Rochester Biology )

Abstract:
tRNAs are heavily modified, and these modifications are essential for accurate decoding and protein synthesis. Among all tRNA modification enzymes, tRNA methyltransferase 1 (TRMT1) adds one or two methyl groups to guanine-26 of tRNAs, generating m²G26 or m²²G26. In humans, among 400 different tRNAs, about two-thirds are modified by TRMT1. Previous studies have shown that depletion of TRMT1 leads to a global decrease in protein synthesis. One potential cause is that aminoacylation of certain cytoplasmic tRNAs depends on TRMT1. However, the effect of TRMT1 in mitochondria remains unknown. Of the 22 human mitochondrial tRNAs, five are substrates of TRMT1. Using northern blotting under acidic conditions, we found that the charging efficiency of mitochondrial tRNA-Ile decreases in TRMT1-deficient cells. In addition, TRMT1 interactome analysis by immunoprecipitation proteomics showed that deletion of the mitochondrial targeting sequence disrupts TRMT1 interactions with aminoacyl-tRNA synthetases. Together, these results demonstrate that TRMT1 plays an important role in maintaining tRNA charging efficiency.

References:
Dewe JM, Fuller BL, Lentini JM, Kellner SM, Fu D. TRMT1-Catalyzed tRNA Modifications Are Required for Redox Homeostasis To Ensure Proper Cellular Proliferation and Oxidative Stress Survival. Mol Cell Biol. 2017;37(21):e00214-17. Published 2017 Oct 13. doi:10.1128/MCB.00214-17
Suzuki T, Yashiro Y, Kikuchi I, et al. Complete chemical structures of human mitochondrial tRNAs. Nat Commun. 2020;11(1):4269. Published 2020 Aug 28. doi:10.1038/s41467-020-18068-6
Zhang K, Manning AC, Lentini JM, et al. Human TRMT1 and TRMT1L paralogs ensure the proper modification state, stability, and function of tRNAs. Cell Rep. 2025;44(1):115092. doi:10.1016/j.celrep.2024.115092

Keywords: tRNA modification, TRMT1