Trmt2b is a nuclear-encoded enzyme responsible for 5-methyluridine (m5U)-methylation in human mitochondria. It catalyzes m5U54 in mitochondrial tRNAs and m5U429 in 12S rRNA, expanding its substrate repertoire to both tRNA and rRNA [1,3]. RNA modifications by Trmt2b are crucial for the normal function of mitochondrial RNA and potentially related to mitochondrial translation and cellular processes.

In mouse models, inactivation of the Trmt2B gene leads to a reduction in the activity of respiratory chain complexes I, III, and IV, whose subunits are synthesized by the mitochondrial protein-synthesis apparatus [3]. In human cells, knocking-out the gene shows no obvious phenotype regarding RNA stability, mitochondrial translation, or cellular growth [1]. In addition, in a family with two juvenile amyotrophic lateral sclerosis (JALS) patients, a variation within TRMT2B (c.1356G>T; p.K452N) was associated with ALS. Functional studies in patient-originated lymphoblastoid cell lines and TRMT2B-interfering HEK293 cells showed decreased mitochondria-related functions and increased ROS levels [2].

In conclusion, Trmt2b is essential for m5U-methylation in mitochondrial tRNA and rRNA. Mouse gene-knockout models have revealed its role in maintaining the activity of mitochondrial respiratory chain complexes. Its association with JALS through gene variations indicates its potential importance in neurodegenerative disease mechanisms, highlighting the significance of Trmt2b research in understanding mitochondrial-related biological processes and neurodegenerative diseases [2,3].

References:

1. Powell, Christopher A, Minczuk, Michal. 2020. TRMT2B is responsible for both tRNA and rRNA m5U-methylation in human mitochondria. In RNA biology, 17, 451-462. doi:10.1080/15476286.2020.1712544. https://pubmed.ncbi.nlm.nih.gov/31948311/

2. Liu, Yanling, He, Xi, Yuan, Yanchun, Hu, Zhengmao, Wang, Junling. 2023. Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis. In Frontiers of medicine, 18, 68-80. doi:10.1007/s11684-023-1005-y. https://pubmed.ncbi.nlm.nih.gov/37874476/

3. Laptev, Ivan, Shvetsova, Ekaterina, Levitskii, Sergey, Sergiev, Petr, Dontsova, Olga. 2019. Mouse Trmt2B protein is a dual specific mitochondrial metyltransferase responsible for m5U formation in both tRNA and rRNA. In RNA biology, 17, 441-450. doi:10.1080/15476286.2019.1694733. https://pubmed.ncbi.nlm.nih.gov/31736397/