An aminoacylation independent activity of PheRS/FARS promotes growth and proliferation

Abstract

Aminoacyl tRNA synthetases (aaRSs) not only load the appropriate amino acid onto their cognate tRNA, but many of them also perform additional functions that are not necessarily related to their canonical activities. Phenylalanyl tRNA synthetase (PheRS/FARS) levels are elevated in multiple cancers compared to their normal cell counterparts. Our results now show that downregulation of PheRS, or only its -PheRS subunit, reduces organ size, whereas elevated expression of the -PheRS subunit stimulates cell growth and proliferation. In the wing discs system, this can lead to a 67% increase of cells that stain for a mitotic marker. Clonal analysis of twin spots in the follicle cells of the ovary revealed that the elevated expression of the -PheRS subunit causes cells to grow and proliferate about 25% faster than their normal twin cells. And this faster growth and proliferation did not affect the size distribution of the proliferating cells. Importantly, this stimulation proliferation turned out to be independent of the β-PheRS subunit and the aminoacylation activity, and it did not visibly stimulate translation.