{"title":"不稳定的β-PheRS对食物回避、生长和发育的影响受到食欲激素CCHa2的抑制。","authors":"Dominique Brunßen, Beat Suter","doi":"10.1080/19336934.2024.2308737","DOIUrl":null,"url":null,"abstract":"<p><p>Amino acyl-tRNA synthetases perform diverse non-canonical functions aside from their essential role in charging tRNAs with their cognate amino acid. The phenylalanyl-tRNA synthetase (PheRS/FARS) is an α<sub>2</sub>β<sub>2</sub> tetramer that is needed for charging the tRNA<sup>Phe</sup> for its translation activity. Fragments of the α-subunit have been shown to display an additional, translation-independent, function that activates growth and proliferation and counteracts Notch signalling. Here we show in <i>Drosophila</i> that overexpressing the β-subunit in the context of the complete PheRS leads to larval roaming, food avoidance, slow growth, and a developmental delay that can last several days and even prevents pupation. These behavioural and developmental phenotypes are induced by PheRS expression in CCHa2<sup>+</sup> and Pros<sup>+</sup> cells. Simultaneous expression of β-PheRS, α-PheRS, and the appetite-inducing CCHa2 peptide rescued these phenotypes, linking this <i>β-PheRS</i> activity to the appetite-controlling pathway. The fragmentation dynamic of the excessive β-PheRS points to β-PheRS fragments as possible candidate inducers of these phenotypes. Because fragmentation of human FARS has also been observed in human cells and mutations in human <i>β-PheRS (FARSB)</i> can lead to problems in gaining weight, Drosophila <i>β-PheRS</i> can also serve as a model for the human phenotype and possibly also for obesity.</p>","PeriodicalId":12128,"journal":{"name":"Fly","volume":"18 1","pages":"2308737"},"PeriodicalIF":2.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880493/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2.\",\"authors\":\"Dominique Brunßen, Beat Suter\",\"doi\":\"10.1080/19336934.2024.2308737\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Amino acyl-tRNA synthetases perform diverse non-canonical functions aside from their essential role in charging tRNAs with their cognate amino acid. The phenylalanyl-tRNA synthetase (PheRS/FARS) is an α<sub>2</sub>β<sub>2</sub> tetramer that is needed for charging the tRNA<sup>Phe</sup> for its translation activity. Fragments of the α-subunit have been shown to display an additional, translation-independent, function that activates growth and proliferation and counteracts Notch signalling. Here we show in <i>Drosophila</i> that overexpressing the β-subunit in the context of the complete PheRS leads to larval roaming, food avoidance, slow growth, and a developmental delay that can last several days and even prevents pupation. These behavioural and developmental phenotypes are induced by PheRS expression in CCHa2<sup>+</sup> and Pros<sup>+</sup> cells. Simultaneous expression of β-PheRS, α-PheRS, and the appetite-inducing CCHa2 peptide rescued these phenotypes, linking this <i>β-PheRS</i> activity to the appetite-controlling pathway. The fragmentation dynamic of the excessive β-PheRS points to β-PheRS fragments as possible candidate inducers of these phenotypes. Because fragmentation of human FARS has also been observed in human cells and mutations in human <i>β-PheRS (FARSB)</i> can lead to problems in gaining weight, Drosophila <i>β-PheRS</i> can also serve as a model for the human phenotype and possibly also for obesity.</p>\",\"PeriodicalId\":12128,\"journal\":{\"name\":\"Fly\",\"volume\":\"18 1\",\"pages\":\"2308737\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10880493/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Fly\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/19336934.2024.2308737\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/2/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Fly","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/19336934.2024.2308737","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/2/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2.
Amino acyl-tRNA synthetases perform diverse non-canonical functions aside from their essential role in charging tRNAs with their cognate amino acid. The phenylalanyl-tRNA synthetase (PheRS/FARS) is an α2β2 tetramer that is needed for charging the tRNAPhe for its translation activity. Fragments of the α-subunit have been shown to display an additional, translation-independent, function that activates growth and proliferation and counteracts Notch signalling. Here we show in Drosophila that overexpressing the β-subunit in the context of the complete PheRS leads to larval roaming, food avoidance, slow growth, and a developmental delay that can last several days and even prevents pupation. These behavioural and developmental phenotypes are induced by PheRS expression in CCHa2+ and Pros+ cells. Simultaneous expression of β-PheRS, α-PheRS, and the appetite-inducing CCHa2 peptide rescued these phenotypes, linking this β-PheRS activity to the appetite-controlling pathway. The fragmentation dynamic of the excessive β-PheRS points to β-PheRS fragments as possible candidate inducers of these phenotypes. Because fragmentation of human FARS has also been observed in human cells and mutations in human β-PheRS (FARSB) can lead to problems in gaining weight, Drosophila β-PheRS can also serve as a model for the human phenotype and possibly also for obesity.
期刊介绍:
Fly is the first international peer-reviewed journal to focus on Drosophila research. Fly covers a broad range of biological sub-disciplines, ranging from developmental biology and organogenesis to sensory neurobiology, circadian rhythm and learning and memory, to sex determination, evolutionary biology and speciation. We strive to become the “to go” resource for every researcher working with Drosophila by providing a forum where the specific interests of the Drosophila community can be discussed. With the advance of molecular technologies that enable researchers to manipulate genes and their functions in many other organisms, Fly is now also publishing papers that use other insect model systems used to investigate important biological questions.
Fly offers a variety of papers, including Original Research Articles, Methods and Technical Advances, Brief Communications, Reviews and Meeting Reports. In addition, Fly also features two unconventional types of contributions, Counterpoints and Extra View articles. Counterpoints are opinion pieces that critically discuss controversial papers questioning current paradigms, whether justified or not. Extra View articles, which generally are solicited by Fly editors, provide authors of important forthcoming papers published elsewhere an opportunity to expand on their original findings and discuss the broader impact of their discovery. Extra View authors are strongly encouraged to complement their published observations with additional data not included in the original paper or acquired subsequently.