Gen Zheng, Wei Liu, Yanhua Gong, Hongbo Yang, Bin Yin, Jingxi Zhu, Yi Xie, Xiaozhong Peng, Boqin Qiang, Jiangang Yuan
The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
The Biochemical journal 2009 Jan 1DTD (D-Tyr-tRNA(Tyr) deacylase) is known to be able to deacylate D-aminoacyl-tRNAs into free D-amino acids and tRNAs and therefore contributes to cellular resistance against D-amino acids in Escherichia coli and yeast. We have found that h-DTD (human DTD) is enriched in the nuclear envelope region of mammalian cells. Treatment of HeLa cells with D-Tyr resulted in nuclear accumulation of tRNA(Tyr). D-Tyr treatment and h-DTD silencing caused tRNA(Tyr) downregulation. Furthermore, inhibition of protein synthesis by D-Tyr treatment and h-DTD silencing were also observed. D-Tyr, D-Asp and D-Ser treatment inhibited mammalian cell viability in a dose-dependent manner; overexpression of h-DTD decreased the inhibition rate, while h-DTD-silenced cells became more sensitive to the D-amino acid treatment. Our results suggest that h-DTD may play an important role in cellular resistance against D-amino acids by deacylating D-aminoacyl tRNAs at the nuclear pore. We have also found that m-DTD (mouse DTD) is specifically enriched in central nervous system neurons, its nuclear envelope localization indicates that D-aminoacyl-tRNA editing may be vital for the survival of neurons under high concentration of D-amino acids.
Gen Zheng, Wei Liu, Yanhua Gong, Hongbo Yang, Bin Yin, Jingxi Zhu, Yi Xie, Xiaozhong Peng, Boqin Qiang, Jiangang Yuan. Human D-Tyr-tRNA(Tyr) deacylase contributes to the resistance of the cell to D-amino acids. The Biochemical journal. 2009 Jan 1;417(1):85-94
PMID: 18700836
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