THG1L Human

THG1L encodes a mitochondrial protein that is essential for the proper recognition and fidelity of protein synthesis. The primary function of THG1L is to catalyze the addition of a guanine nucleotide (GMP) to the 5’-end of tRNA-His after transcription and RNase P cleavage . This step is vital for the accurate recognition of tRNA-His by histidyl-tRNA synthetase (HisRS), ensuring the correct incorporation of histidine during protein synthesis .

Additionally, THG1L functions as a guanyl-nucleotide exchange factor (GEF) for the mitofusins MFN1 and MFN2, thereby regulating mitochondrial fusion. By influencing mitochondrial dynamics and bioenergetic function, THG1L contributes to cell survival following oxidative stress .

THG1L is associated with several diseases, including Spinocerebellar Ataxia, Autosomal Recessive 28, and Renal Fibrosis . The protein encoded by this gene is induced by high levels of glucose and is linked to diabetic nephropathy. Increased expression of THG1L appears to enhance mitochondrial biogenesis, which could lead to renal fibrosis .

The THG1L gene is located on chromosome 5q33.3 and consists of several transcript variants encoding different isoforms . The protein has a predicted molecular mass of approximately 34.8 kDa and contains multiple potential post-translational modification sites, including N-glycosylation, tyrosine sulfation, phosphorylation, N-myristoylation, and amidation sites .

Research on THG1L has revealed its importance in various cellular processes. Knockdown studies in HeLa cells have shown that reduced expression of THG1L inhibits cell growth and proliferation, leading to quiescent cells with polycentrosomes, multiple nuclei, upregulated expression of p53, and increased apoptosis . These findings highlight the potential therapeutic implications of targeting THG1L in diseases related to mitochondrial dysfunction and oxidative stress.