The Caenorhabditis elegans proteasome subunit RPN-12 is required for hermaphrodite germline sex determination and oocyte quality.

摘要

Background: The proteasome is a multi-subunit complex and a major proteo-lytic machinery in cells. Most subunits are essential for proteasome function, and depletion of individual subunits normally results in lethality. RPN-12/ Rpn12/PSMD8 is a lid subunit of the 19S regulatory particle (RP) of the 26S proteasome. Studies in Caenorhabditis elegans demonstrated that RNAi depletion of RPN-12 does not result in lethality. RPN-12 has not been well studied in higher eukaryotes. In this study, we investigate the biological significance of RPN-12 in C. elegans. Results: We found that the null mutant rpn-12(av93) did not cause major impairment of the proteolytic activity of the proteasome. Most rpn-12(av93) hermaphrodites lack sperm leading to feminization of the germ line that can be partially rescued by mating to males. The lack of sperm phenotype can be suppressed by downregulation of TRA-1, a player in the hermaphrodite germline sex determination pathway. Also, rpn-12(av93) animals show significant nuclear accumulation of the meiotic kinase WEE-1.3, a protein predominantly localized to the perinuclear region. Interestingly, chemical inhibition of the proteasome did not cause nuclear accumulation of WEE-1.3. Conclusions: RPN-12 plays a previously unknown role in oogenesis and the germline sex determination pathway in C. elegans hermaphrodites.