UBR4 deficiency causes male sterility and developmental delay

Author:

Xie Shi-Ming1,Lai Jia-Xuan1,Liu Chu-Qiao2,Zhang Xi-Xing2,Lin Yong-Miao2,Chen Xiao-Chuan3,Qiao Jing-Da1,Mao Yu-Ling4

Affiliation:

1. Department of Neurology, Institute of Neuroscience, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

2. The Second Clinical Medicine School of Guangzhou Medical University, China

3. Department of Obstetrics and Gynecology, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

4. Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory for Reproductive Medicine of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China

Abstract

Abstract 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.

Publisher

Research Square Platform LLC

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