Post-transcriptional regulation ofcyclin Aandcyclin BmRNAs is mediated by Bruno 1 and Cup, and further fine-tuned within P-bodies

Abstract

Cell cycle progression is tightly controlled by the regulated synthesis and degradation of Cyclins, such as Cyclin A and Cyclin B, which activate CDK1 to trigger mitosis. Mutations affecting Cyclin regulation are often linked to tumorigenesis, making the study of cyclin mRNA regulation critical for identifying new cancer therapies. In this study, we demonstrate via super-resolution microscopy that cyclin A and cyclin B mRNAs associate with Bruno 1 and Cup in nurse cells. Depletion of either protein leads to abnormal Cyclin A and Cyclin B protein expression and a reduction in mRNA levels for both Cyclins. We further reveal that both cyclin A and cyclin B mRNAs accumulate in P-bodies marked by Me31B. Interestingly, Me31B is not involved in regulating cyclin A mRNA, as no changes in cyclin A mRNA levels or repression were observed upon Me31B depletion. However, cyclin B mRNA shows stage-specific derepression and reduced levels when Me31B is absent. Notably, the association between cyclin B and Cup is strengthened in the absence of Me31B, indicating that this interaction occurs independently of P-bodies. These results highlight the nuanced, mRNA-specific roles of P-body condensates in post-transcriptional regulation, challenging the idea of a uniform, binary mechanism of mRNA repression in P-bodies.