UBR4 deficiency causes male sterility and developmental delay

It has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility and development with a drosophila model. Different UBR4 knockdown flies were established using the GAL4/upstream activating sequence system. Fertility, hatchability and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could promote larvae developmental delay and male drosophila fertility. We found that UBR4 deficiency affected the testis during morphological analysis. Bioinformatics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of UBR4 knockdown flies. Gene Ontology analysis revealed that significant upregulation of Sfp65A and downregulation of Pelota were involved in the reproductive process in drosophila , important in testis generation and sperm storage promotion. Overall, our findings suggest that UBR4 deficiency could promote male infertility in drosophila and may be involved in the protein modification of UBR4 by upregulating Sfp65A anddownregulating Pelota protein expression.