UPRT, a suicide-gene therapy candidate in higher eukaryotes, is required for Drosophila larval growth and normal adult lifespan

Arpan C. Ghosh, Maryjane Shimell, Emma R. Leof, Macy J. Haley, Michael B. O'Connor

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Uracil phosphoribosyltransferase (UPRT) is a pyrimidine salvage pathway enzyme that catalyzes the conversion of uracil to uridine monophosphate (UMP). The enzyme is highly conserved from prokaryotes to humans and yet phylogenetic evidence suggests that UPRT homologues from higher-eukaryotes, including Drosophila, are incapable of binding uracil. Purified human UPRT also do not show any enzymatic activity in vitro, making microbial UPRT an attractive candidate for anti-microbial drug development, suicide-gene therapy, and cell-specific mRNA labeling techniques. Nevertheless, the enzymatic site of UPRT remains conserved across the animal kingdom indicating an in vivo role for the enzyme. We find that the Drosophila UPRT homologue, krishah (kri), codes for an enzyme that is required for larval growth, pre-pupal/pupal viability and long-term adult lifespan. Our findings suggest that UPRT from all higher eukaryotes is likely enzymatically active in vivo and challenges the previous notion that the enzyme is non-essential in higher eukaryotes and cautions against targeting the enzyme for therapeutic purposes. Our findings also suggest that expression of the endogenous UPRT gene will likely cause background incorporation when using microbial UPRT as a cell-specific mRNA labeling reagent in higher eukaryotes.

Original languageEnglish (US)
Article number13176
JournalScientific reports
StatePublished - Aug 14 2015

Bibliographical note

Funding Information:
We thank Aidan Peterson for critical comments on the manuscript and Michael Cleary and Chris Doe for advice and reagents. We thank Roger E. Karess for the Δmad2 deletion stock. This work was supported in part by R01 GM 093301 and R01 GM095746 to M.B.O. and a predoctoral fellowship from the American Heart Association to A.C.G.

Fingerprint Dive into the research topics of 'UPRT, a suicide-gene therapy candidate in higher eukaryotes, is required for Drosophila larval growth and normal adult lifespan'. Together they form a unique fingerprint.

Cite this