C57BL/6JCya-Trmu^em1/Cya

Trmu, or tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase, is a nuclear gene crucial for mitochondrial DNA translation. It thiolates mitochondrial tRNA, playing a vital role in mitochondrial function. The process it participates in is integral to maintaining normal mitochondrial activity and is thus important for overall cellular function [1,2,3,4,5,6].

Biallelic pathogenic variants in TRMU are associated with a range of clinical manifestations. Transient infantile liver failure is a common presentation, and other less common ones include Leigh syndrome, myopathy, and cardiomyopathy [1,2,3]. In a study of 62 individuals with biallelic (likely) pathogenic TRMU variants, liver involvement was highly prevalent, and acute liver failure (ALF) occurred only in the first year of life in many cases. Loss-of-function TRMU variants were associated with poor survival, but cysteine supplementation improved survival significantly [2]. Also, reduced TRMU expression in hair-cell-like HEI-OC-1 cells increased sensitivity to neomycin damage, with increased mitochondrial dysfunction and reactive oxygen species (ROS) levels, and N-acetylcysteine could rescue the induced mitochondrial dysfunction and cell apoptosis [4].

In conclusion, Trmu is essential for mitochondrial tRNA modification and normal mitochondrial function. Studies related to TRMU-associated diseases, especially those involving infantile liver failure, have shown the significance of this gene in disease development. The impact of Trmu on disease phenotypes, such as survival in cases of liver failure and ototoxicity-related cell death, highlights its importance in understanding the underlying mechanisms of these diseases [1,2,3,4].

References:

1. Murali, Chaya N, Soler-Alfonso, Claudia, Loomes, Kathleen M, Scaglia, Fernando, Ganetzky, Rebecca. 2021. TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation. In Molecular genetics and metabolism, 132, 146-153. doi:10.1016/j.ymgme.2021.01.005. https://pubmed.ncbi.nlm.nih.gov/33485800/

2. Vogel, Georg F, Mozer-Glassberg, Yael, Landau, Yuval E, Weghuber, Daniel, Wortmann, Saskia. 2022. Genotypic and phenotypic spectrum of infantile liver failure due to pathogenic TRMU variants. In Genetics in medicine : official journal of the American College of Medical Genetics, 25, 100314. doi:10.1016/j.gim.2022.09.015. https://pubmed.ncbi.nlm.nih.gov/36305855/

3. Sala-Coromina, Júlia, Miguel, Lucía Dougherty-de, de Las Heras, Javier, Tort, Frederic, Del Toro, Mireia. 2020. Leigh syndrome associated with TRMU gene mutations. In Molecular genetics and metabolism reports, 26, 100690. doi:10.1016/j.ymgmr.2020.100690. https://pubmed.ncbi.nlm.nih.gov/33365252/

4. He, Zuhong, Sun, Shan, Waqas, Muhammad, Li, Huawei, Chai, Renjie. 2016. Reduced TRMU expression increases the sensitivity of hair-cell-like HEI-OC-1 cells to neomycin damage in vitro. In Scientific reports, 6, 29621. doi:10.1038/srep29621. https://pubmed.ncbi.nlm.nih.gov/27405449/

5. Chen, Chao, Guan, Min-Xin. . Genetic correction of TRMU allele restored the mitochondrial dysfunction-induced deficiencies in iPSCs-derived hair cells of hearing-impaired patients. In Human molecular genetics, 31, 3068-3082. doi:10.1093/hmg/ddac096. https://pubmed.ncbi.nlm.nih.gov/35467742/

6. Yan, Qingfeng, Bykhovskaya, Yelena, Li, Ronghua, Fischel-Ghodsian, Nathan, Guan, Min-Xin. 2006. Human TRMU encoding the mitochondrial 5-methylaminomethyl-2-thiouridylate-methyltransferase is a putative nuclear modifier gene for the phenotypic expression of the deafness-associated 12S rRNA mutations. In Biochemical and biophysical research communications, 342, 1130-6. doi:. https://pubmed.ncbi.nlm.nih.gov/16513084/