Tsr1, also known as pre-rRNA-processing protein TSR1 homolog, is involved in ribosome biogenesis. It has sequence similarity to GTPases, yet lacks the active site residues for GTP binding and hydrolysis [4]. It is essential for cytoplasmic steps in 40S subunit maturation, potentially preventing premature binding to 60S subunits due to its highly acidic surface presented on the outside of pre-40S particles [4].

In a Chinese congenital cataract family, a novel TSR1 mutation was identified. The TSR1 c.202-1G>A substitution affected splicing of TSR1 mRNA. Tsr1 was expressed in mouse lens, anterior lens capsule of age-related cataract patients and 24-week human fetal lens. GO function analysis indicated Tsr1 might play a role in the MAPK-Erk signaling pathway in addition to ribosome assembly [3]. In the context of liver injury, tRF-Gln-CTG-026 ameliorates liver injury by repressing global protein synthesis through the weakened association between TSR1 and pre-40S ribosome [1]. Also, in the Chinese Han population, TSR1 was identified as a potential causal gene for spontaneous coronary artery dissection (SCAD). All TSR1 germline variants were either highly conserved across distinct species or led to premature termination of protein syntheses, and TSR1 expression was detectable in human coronary artery tissues [2].

In conclusion, Tsr1 is crucial for ribosome biogenesis and has implications in multiple biological processes and disease conditions. Its role in congenital cataract, liver injury, and SCAD has been revealed through various studies, with the findings from these genetic-based research models contributing to our understanding of the underlying mechanisms in these disease areas.

References:

1. Ying, Sunyang, Li, Pengcheng, Wang, Jiaqiang, Zhang, Ying, Zhou, Qi. 2023. tRF-Gln-CTG-026 ameliorates liver injury by alleviating global protein synthesis. In Signal transduction and targeted therapy, 8, 144. doi:10.1038/s41392-023-01351-5. https://pubmed.ncbi.nlm.nih.gov/37015921/

2. Sun, Yang, Chen, Yanghui, Li, Yuanyuan, Dou, Kefei, Wang, Dao Wen. . Association of TSR1 Variants and Spontaneous Coronary Artery Dissection. In Journal of the American College of Cardiology, 74, 167-176. doi:10.1016/j.jacc.2019.04.062. https://pubmed.ncbi.nlm.nih.gov/31296287/

3. Yu, Ya-Jie, Qiu, Feng, Zhang, Xin-An. . Studies of congenital cataract-related TSR1 mutation and its expression in the lens. In Yi chuan = Hereditas, 42, 161-171. doi:10.16288/j.yczz.19-166. https://pubmed.ncbi.nlm.nih.gov/32102773/

4. McCaughan, Urszula M, Jayachandran, Uma, Shchepachev, Vadim, Tollervey, David, Cook, Atlanta G. 2016. Pre-40S ribosome biogenesis factor Tsr1 is an inactive structural mimic of translational GTPases. In Nature communications, 7, 11789. doi:10.1038/ncomms11789. https://pubmed.ncbi.nlm.nih.gov/27250689/