Human D-Tyr-tRNA(Tyr) deacylase contributes to the resistance of the cell to D-amino acids.
DTD (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.
Zheng
Gen
G
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.
Liu
Wei
W
Gong
Yanhua
Y
Yang
Hongbo
H
Yin
Bin
B
Zhu
Jingxi
J
Xie
Yi
Y
Peng
Xiaozhong
X
Qiang
Boqin
B
Yuan
Jiangang
J
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000378:metabolism; D004351:Drug Resistance; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D000596:Amino Acids; D012346:RNA, Transfer, Amino Acyl; D019881:Aminoacyltransferases; C120167:D-tyrosine tRNA(Tyr) deacylase