Bayer Livia V, Milano Samantha N, Kaur Harpreet, Bratu Diana P
Department of Biological Sciences, Hunter College, City University of New York, New York, NY, 10065 USA.
Program in Molecular, Cellular, and Developmental Biology, The Graduate Center, City University of New York, New York, NY, 10016 USA.
bioRxiv. 2024 Nov 21:2024.10.17.618951. doi: 10.1101/2024.10.17.618951.
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 and mRNAs associate with Bruno 1 and Cup in nurse cells. The 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 and mRNAs accumulate in P-bodies marked by Me31B. Interestingly, Me31B is not involved in regulating mRNA, as no changes in mRNA levels or repression are observed upon Me31B depletion. However, mRNA shows stage-specific derepression and reduced levels when Me31B is absent. Notably, the association between 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.
细胞周期进程受到细胞周期蛋白(如细胞周期蛋白A和细胞周期蛋白B)合成与降解的严格调控,这些细胞周期蛋白激活细胞周期蛋白依赖性激酶1(CDK1)以触发有丝分裂。影响细胞周期蛋白调控的突变通常与肿瘤发生相关,这使得研究细胞周期蛋白mRNA调控对于确定新的癌症治疗方法至关重要。在本研究中,我们通过超分辨率显微镜证明,细胞周期蛋白A和细胞周期蛋白B的mRNA在滋养细胞中与布鲁诺1(Bruno 1)和Cup蛋白相关联。去除这两种蛋白质中的任何一种都会导致细胞周期蛋白A和细胞周期蛋白B的蛋白质表达异常以及这两种细胞周期蛋白的mRNA水平降低。我们进一步发现,细胞周期蛋白A和细胞周期蛋白B的mRNA都在由Me31B标记的加工小体中积累。有趣的是,Me31B不参与调控细胞周期蛋白A的mRNA,因为在去除Me31B后未观察到细胞周期蛋白A的mRNA水平或抑制作用发生变化。然而,当不存在Me31B时,细胞周期蛋白B的mRNA表现出阶段特异性的去抑制和水平降低。值得注意的是,在不存在Me31B的情况下,细胞周期蛋白B的mRNA与Cup的关联增强,表明这种相互作用独立于加工小体发生。这些结果突出了加工小体凝聚物在转录后调控中对mRNA具有细微、特异性的作用,挑战了加工小体中mRNA抑制的统一、二元机制这一观点。