TARS1, encoding cytoplasmic threonyl-tRNA synthetase, is an essential enzyme that ligates threonine to tRNATHR in the cytoplasm, playing a fundamental role in the first step of protein translation [3,4]. Aminoacyl-tRNA synthetases, including TARS1, are also involved in non-translational functions such as the regulation of gene expression, cell signaling, angiogenesis, inflammatory responses, and tumorigenesis [2]. Genetic models like yeast, worms, and mice are valuable for studying TARS1.

In breast cancer, TARS1 is overexpressed and associated with poor prognoses. It promotes the infiltration of Tregs and Th2s, while inhibiting the infiltration of anticancer cells like NK cells and CD8+ T cells. Knocking down TARS1 prevents breast cancer cells from proliferating and invading, suggesting it may be an oncogene and a potential biomarker or immunotherapy target [1]. In a compound heterozygous mouse model (R433H/null) mimicking TARS1-related recessive phenotypes, distinct lung and skin defects were observed, expanding the understanding of the clinical heterogeneity of TARS1-related recessive disease [3,4]. Homozygous Tars1 KO mice were lethal, indicating Tars1 is an essential gene [5].

In summary, TARS1 is crucial for protein translation and has non-translational functions in multiple cellular processes. Mouse models, especially KO models, have provided insights into its role in diseases such as breast cancer and recessive disorders, enhancing our understanding of its biological functions and potential implications for human health.

References:

1. Gui, Zhengwei, Liu, Piao, Zhang, Dong, Wang, Wanju. 2023. Clinical implications and immune implications features of TARS1 in breast cancer. In Frontiers in oncology, 13, 1207867. doi:10.3389/fonc.2023.1207867. https://pubmed.ncbi.nlm.nih.gov/37637061/

2. Barai, Pallob, Chen, Jie. . Beyond protein synthesis: non-translational functions of threonyl-tRNA synthetases. In Biochemical Society transactions, 52, 661-670. doi:10.1042/BST20230506. https://pubmed.ncbi.nlm.nih.gov/38477373/

3. Meyer-Schuman, Rebecca, Cale, Allison R, Pierluissi, Jennifer A, Meisler, Miriam H, Antonellis, Anthony. 2024. A model organism pipeline provides insight into the clinical heterogeneity of TARS1 loss-of-function variants. In HGG advances, 5, 100324. doi:10.1016/j.xhgg.2024.100324. https://pubmed.ncbi.nlm.nih.gov/38956874/

4. Meyer-Schuman, Rebecca, Cale, Allison R, Pierluissi, Jennifer A, Meisler, Miriam H, Antonellis, Anthony. 2024. Predictive modeling provides insight into the clinical heterogeneity associated with TARS1 loss-of-function mutations. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.03.25.586600. https://pubmed.ncbi.nlm.nih.gov/38585737/

5. Zeng, Qi-Yu, Zhang, Fan, Zhang, Jian-Hui, Sun, Xiao-Jian, Zhou, Xiao-Long. 2023. Loss of threonyl-tRNA synthetase-like protein Tarsl2 has little impact on protein synthesis but affects mouse development. In The Journal of biological chemistry, 299, 104704. doi:10.1016/j.jbc.2023.104704. https://pubmed.ncbi.nlm.nih.gov/37059185/