دورية أكاديمية
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TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice.

التفاصيل البيبلوغرافية
العنوان: TRMT10A dysfunction perturbs codon translation of initiator methionine and glutamine and impairs brain functions in mice.
المؤلفون: Tresky R; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Miyamoto Y; Department of Anatomy and Neurobiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Nagayoshi Y; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.; Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Yabuki Y; Department of Genomic Neurology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan., Araki K; Division of Developmental Genetics, Institute of Resource Development and Analysis, Kumamoto University, Kumamoto 860-0811, Japan., Takahashi Y; Department of Anatomy and Neurobiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Komohara Y; Department of Cell Pathology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Ge H; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Nishiguchi K; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.; Department of Nephrology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Fukuda T; Department of Anatomy and Neurobiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Kaneko H; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Maeda N; Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Matsuura J; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.; Department of Neurosurgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Iwasaki S; RNA Systems Biochemistry Laboratory, RIKEN Cluster for Pioneering Research, Saitama 351-0198, Japan.; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan., Sakakida K; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.; Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Shioda N; Department of Genomic Neurology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan., Wei FY; Department of Modomics Biology and Medicine, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan., Tomizawa K; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan., Chujo T; Department of Molecular Physiology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
المصدر: Nucleic acids research [Nucleic Acids Res] 2024 Aug 27; Vol. 52 (15), pp. 9230-9246.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Brain*/metabolism , Glutamine*/metabolism , Protein Biosynthesis* , tRNA Methyltransferases*/genetics , tRNA Methyltransferases*/metabolism, Animals ; Humans ; Male ; Mice ; Codon/genetics ; Mice, Inbred C57BL ; Mice, Knockout ; Ribosomes/metabolism ; Ribosomes/genetics ; RNA, Transfer, Met/metabolism ; RNA, Transfer, Met/genetics
مستخلص: In higher eukaryotes, tRNA methyltransferase 10A (TRMT10A) is responsible for N1-methylguanosine modification at position nine of various cytoplasmic tRNAs. Pathogenic mutations in TRMT10A cause intellectual disability, microcephaly, diabetes, and short stature in humans, and generate cytotoxic tRNA fragments in cultured cells; however, it is not clear how TRMT10A supports codon translation or brain functions. Here, we generated Trmt10a null mice and showed that tRNAGln(CUG) and initiator methionine tRNA levels were universally decreased in various tissues; the same was true in a human cell line lacking TRMT10A. Ribosome profiling of mouse brain revealed that dysfunction of TRMT10A causes ribosome slowdown at the Gln(CAG) codon and increases translation of Atf4 due to higher frequency of leaky scanning of its upstream open reading frames. Broadly speaking, translation of a subset of mRNAs, especially those for neuronal structures, is perturbed in the mutant brain. Despite not showing discernable defects in the pancreas, liver, or kidney, Trmt10a null mice showed lower body weight and smaller hippocampal postsynaptic densities, which is associated with defective synaptic plasticity and memory. Taken together, our study provides mechanistic insight into the roles of TRMT10A in the brain, and exemplifies the importance of universal tRNA modification during translation of specific codons.
(© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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معلومات مُعتمدة: JPMJFR204Z Fusion Oriented REsearch for Disruptive Science and Technology; 21H02731 Japan Science and Technology Agency; Japan Society for the Promotion of Science; Takeda Science Foundation; Kumamoto University Center for Metabolic Regulation of Healthy Aging (CMHA)
المشرفين على المادة: 0 (Codon)
0RH81L854J (Glutamine)
0 (RNA, Transfer, Met)
EC 2.1.1.- (tRNA Methyltransferases)
EC 2.1.1.- (TRMT10A protein, human)
تواريخ الأحداث: Date Created: 20240701 Date Completed: 20240827 Latest Revision: 20240829
رمز التحديث: 20240830
مُعرف محوري في PubMed: PMC11347157
DOI: 10.1093/nar/gkae520
PMID: 38950903
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkae520