Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2.

IF 2.4 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Fly Pub Date : 2024-12-01 Epub Date: 2024-02-19 DOI:10.1080/19336934.2024.2308737
Dominique Brunßen, Beat Suter
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引用次数: 0

Abstract

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.

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。
氨基酸酰基-tRNA 合成酶除了在 tRNA 中充填同源氨基酸的重要作用外,还具有多种非规范功能。苯丙氨酰-tRNA 合成酶(PheRS/FARS)是一种 α2β2 四聚体,它需要为 tRNAPhe 充电,以便其进行翻译活动。α亚基的片段已被证明具有额外的、不依赖于翻译的功能,可激活生长和增殖并抵消 Notch 信号。在这里,我们在果蝇中发现,在完整的 PheRS 背景下过量表达 β 亚基会导致幼虫漫游、回避食物、生长缓慢以及发育延迟,这种延迟可持续数天,甚至会阻碍化蛹。在 CCHa2+ 和 Pros+ 细胞中表达 PheRS 会诱发这些行为和发育表型。同时表达β-PheRS、α-PheRS和诱导食欲的CCHa2肽可挽救这些表型,从而将β-PheRS活性与食欲控制途径联系起来。过量β-PheRS的破碎动态表明,β-PheRS片段可能是这些表型的候选诱导剂。由于在人类细胞中也观察到了人类 FARS 的破碎,而且人类 β-PheRS(FARSB)的突变会导致体重增加的问题,因此果蝇 β-PheRS 也可以作为人类表型的模型,也可能是肥胖症的模型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Fly
Fly 生物-生化与分子生物学
CiteScore
2.90
自引率
0.00%
发文量
17
审稿时长
>12 weeks
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.
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