Deubiquitylating (DUB) enzymes free covalently linked ubiquitin moieties from ubiquitin-ubiquitin
and ubiquitin-protein conjugates, and thereby maintain the equilibrium between free
and conjugated ubiquitin moieties and regulate ubiquitin-mediated cellular processes.
Here, we performed genetic analyses of mutant phenotypes in Drosophila melanogaster
and demonstrate that loss of Usp14 function results in male sterility, with defects
in spermatid individualization and reduced testicular free monoubiquitin levels. These
phenotypes were rescued by germline-specific overexpression of wild-type Usp14. Synergistic
genetic interactions with Ubi-p63E and cycloheximide sensitivity suggest that ubiquitin
shortage is a primary cause of male sterility. In addition, Usp14 is predominantly
expressed in testes in Drosophila, indicating a higher demand for this DUB in testes
that is also reflected by testis-specific loss-of-function Usp14 phenotypes. Collectively,
these results suggest a major role of Usp14 in maintaining normal steady state free
monoubiquitin levels during the later stages of Drosophila spermatogenesis.This article
has an associated First Person interview with the first author of the paper.