Abstract
The housekeeping tRNA synthetases play many non-canonical roles with diverse functions. The phenylalanyl-tRNA synthetase (PheRS/FARS) is an α2β2 tetramere. Recently, human patients with mutations in FARSB, the homolog of β-PheRS in Drosophila, have been reported to display problems gaining weight. 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. Narrowing down the tissue involved in this behavioral and developmental effect revealed that expression in CCHa2+ and Pros+ cells induced this phenotype. 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 dynamics of the excessive β-PheRS points to a β-PheRS fragment as a likely candidate inducer of these phenotypes. Fragmentation of PheRS (FARS) has also been observed in humans and mutations in human β-PheRS (FARSB) can lead to problems in gaining weight. This study, therefore, points to a potential mechanism for the human phenotype and to possible novel approaches to research ways to correct the balance between hunger and satiety signals in the context of obesity.
Competing Interest Statement
The authors have declared no competing interest.