title: Ablation of Arg-tRNA-protein transferases results in defective neural tube development.
abstract: The arginylation branch of the N-end rule pathway is a ubiquitin-mediated proteolytic system in which post-translational conjugation of Arg by ATE1-encoded Arg-tRNA-protein transferase to N-terminal Asp, Glu, or oxidized Cys residues generates essential degradation signals. Here, we characterized the ATE1-/- mice and identified the essential role of N-terminal arginylation in neural tube development. ATE1-null mice showed severe intracerebral hemorrhages and cystic space near the neural tubes. Expression of ATE1 was prominent in the developing brain and spinal cord, and this pattern overlapped with the migration path of neural stem cells. The ATE1-/- brain showed defective G-protein signaling. Finally, we observed reduced mitosis in ATE1-/- neuroepithelium and a significantly higher nitric oxide concentration in the ATE1-/- brain. Our results strongly suggest that the crucial role of ATE1 in neural tube development is directly related to proper turn-over of the RGS4 protein, which participate in the oxygen-sensing mechanism in the cells. [BMB Reports 2016; 49(8): 443-448].
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
authors.forename: Eunkyoung
authors.initials: E
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Seonmu
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
authors.forename: Yong Tae
authors.initials: YT
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine; Department of Biomedical Sciences, Seoul National University Graduate School; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Min Jae
authors.initials: MJ
authors.lastname: Lee
mesh_terms: D000483:Alleles; D019881:Aminoacyltransferases / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D002490:Central Nervous System / Q000473:pathology; D020964:Embryo Loss / Q000201:enzymology / Q000473:pathology; D004622:Embryo, Mammalian / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D008810:Mice, Inbred C57BL; D054259:Neural Tube / Q000002:abnormalities* / Q000196:embryology* / Q000201:enzymology / Q000473:pathology; D046569:Neuroepithelial Cells / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000473:pathology; D011247:Pregnancy; D059748:Proteolysis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D019881:Aminoacyltransferases; C019727:arginyltransferase; D001616:beta-Galactosidase