Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis
| Autor: | Odelia Rajanayagam, Nadia Schoenmakers, Bradley A. Carlson, Erik Schoenmakers, Rachel Peat, Francesco Muntoni, Maura Agostini, Evelien F. Gevers, Pascale Guicheney, Ryuta Tobe, Greta Lyons, Krishna Chatterjee, Carla Moran, Sadaf Farooqi, Dolph L. Hatfield, Elena G. Bochukova |
|---|---|
| Přispěvatelé: | HAL UPMC, Gestionnaire, Wellcome Trust - MRC Cambridge, Molecular Biology of Selenium Section, Bethesda, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Royal London Hospital, Dubowitz Neuromuscular Center, Institute of Child Health, Schoenmakers, Erik [0000-0003-0674-8282], Schoenmakers, Nadia [0000-0002-0847-2884], Chatterjee, Krishna [0000-0002-2654-8854], Apollo - University of Cambridge Repository, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male TRNA modification Mutant DNA Mutational Analysis Molecular Sequence Data Biology medicine.disease_cause Polymorphism Single Nucleotide 03 medical and health sciences chemistry.chemical_compound medicine Protein biosynthesis Humans Point Mutation Child Selenoproteins Genetic Association Studies chemistry.chemical_classification Mutation [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology 030102 biochemistry & molecular biology Selenocysteine Base Sequence Brief Report Point mutation Genetic Diseases Inborn General Medicine RNA Transfer Amino Acid-Specific Molecular biology 3. Good health 030104 developmental biology chemistry Biochemistry Protein Biosynthesis Transfer RNA Selenoprotein [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Journal of Clinical Investigation Journal of Clinical Investigation, 2016, 126 (3), pp.992-996. ⟨10.1172/JCI84747⟩ Journal of Clinical Investigation, American Society for Clinical Investigation, 2016, 126 (3), pp.992-996. ⟨10.1172/JCI84747⟩ |
| ISSN: | 0021-9738 |
| Popis: | International audience; Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome–encoded, transfer RNA (tRNA[Ser]Sec). Here, we have identified a human tRNA[Ser]Sec mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress-related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2′-O-methylribosylation at uridine 34 in mutant tRNA[Ser]Sec. Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA[Ser]Sec. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|