Osgepl1, an ortholog of OSGEP in mitochondria, is a crucial enzyme for the formation of N6-threonylcarbamoyladenosine at A37 (t6A37) in mitochondrial tRNAs [1,2,3,4]. t6A37 modification is essential for translational accuracy and fidelity, and Osgepl1 is involved in the mitochondrial translation pathway [1,2,3,4]. Its proper function is of great significance for mitochondrial gene expression and overall cell function [1,4]. Genetic models, such as gene knockout in cells and mice, are valuable for studying Osgepl1.

In HEK293T cells, deletion of Osgepl1 led to t6A37 hypomodification, which selectively stimulated other tRNA modifications like N1-methyladenosine at A9 (m1A9) and N2-methylguanosine at G10 (m2G10), reduced the aminoacylation of mitochondrial tRNAThr and tRNALys, impaired translation efficiency, and triggered translational infidelity. This also caused alterations in mitochondrial structure, function, and activated the mitochondrial unfolded protein response [1]. In Osgepl1 deletion mice, disruption to mitochondrial translation was evident, but no observable deficiency was seen under physiological conditions in the heart, despite the high Osgepl1 expression in the heart [1]. In addition, in vitro experiments showed that OSGEPL1 is a monomer and its activity is affected by acetylation, and specific tRNA sequences are fine-tuned for different modification levels [2].

In summary, Osgepl1 is vital for maintaining mitochondrial translation efficiency and quality control through t6A37 modification [1]. The gene knockout studies in cells and mice have revealed its role in mitochondrial-related biological processes, though the lack of physiological deficiency in the heart of knockout mice indicates potential compensatory mechanisms. Understanding Osgepl1 may provide insights into mitochondrial-related diseases and translational regulation [1].

References:

1. Zhang, Yong, Zhou, Jing-Bo, Yin, Yue, Wang, En-Duo, Zhou, Xiao-Long. . Multifaceted roles of t6A biogenesis in efficiency and fidelity of mitochondrial gene expression. In Nucleic acids research, 52, 3213-3233. doi:10.1093/nar/gkae013. https://pubmed.ncbi.nlm.nih.gov/38227555/

2. Zhou, Jing-Bo, Wang, Yong, Zeng, Qi-Yu, Wang, En-Duo, Zhou, Xiao-Long. . Molecular basis for t6A modification in human mitochondria. In Nucleic acids research, 48, 3181-3194. doi:10.1093/nar/gkaa093. https://pubmed.ncbi.nlm.nih.gov/32047918/

3. Su, Chenchen, Jin, Mengqi, Zhang, Wenhua. 2022. Conservation and Diversification of tRNA t6A-Modifying Enzymes across the Three Domains of Life. In International journal of molecular sciences, 23, . doi:10.3390/ijms232113600. https://pubmed.ncbi.nlm.nih.gov/36362385/

4. Lin, Huan, Miyauchi, Kenjyo, Harada, Tai, Sakaguchi, Yuriko, Suzuki, Tsutomu. 2018. CO2-sensitive tRNA modification associated with human mitochondrial disease. In Nature communications, 9, 1875. doi:10.1038/s41467-018-04250-4. https://pubmed.ncbi.nlm.nih.gov/29760464/