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

ABSTRACTAmino 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. Fragmen...

Full description

Bibliographic Details
Main Authors: Dominique Brunßen, Beat Suter
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Fly
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/19336934.2024.2308737
_version_ 1797302446053130240
author Dominique Brunßen
Beat Suter
author_facet Dominique Brunßen
Beat Suter
author_sort Dominique Brunßen
collection DOAJ
description ABSTRACTAmino 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.
first_indexed 2024-03-07T23:36:57Z
format Article
id doaj.art-fb1f563512584e86ab495f7cdf8d46e4
institution Directory Open Access Journal
issn 1933-6934
1933-6942
language English
last_indexed 2024-03-07T23:36:57Z
publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series Fly
spelling doaj.art-fb1f563512584e86ab495f7cdf8d46e42024-02-20T06:49:22ZengTaylor & Francis GroupFly1933-69341933-69422024-12-0118110.1080/19336934.2024.2308737Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2Dominique Brunßen0Beat Suter1Institute of Cell Biology, University of Bern, Bern, SwitzerlandInstitute of Cell Biology, University of Bern, Bern, SwitzerlandABSTRACTAmino 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.https://www.tandfonline.com/doi/10.1080/19336934.2024.2308737Drosophiladevelopmental delaygrowthroamingsatiety signaling
spellingShingle Dominique Brunßen
Beat Suter
Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2
Fly
Drosophila
developmental delay
growth
roaming
satiety signaling
title Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2
title_full Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2
title_fullStr Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2
title_full_unstemmed Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2
title_short Effects of unstable β-PheRS on food avoidance, growth, and development are suppressed by the appetite hormone CCHa2
title_sort effects of unstable β phers on food avoidance growth and development are suppressed by the appetite hormone ccha2
topic Drosophila
developmental delay
growth
roaming
satiety signaling
url https://www.tandfonline.com/doi/10.1080/19336934.2024.2308737
work_keys_str_mv AT dominiquebrunßen effectsofunstablebphersonfoodavoidancegrowthanddevelopmentaresuppressedbytheappetitehormoneccha2
AT beatsuter effectsofunstablebphersonfoodavoidancegrowthanddevelopmentaresuppressedbytheappetitehormoneccha2