Cyclin Y-mediated transcript profiling reveals several important functional pathways regulated by Cyclin Y in hippocampal neurons

Cyclin Y (CCNY), which is a cyclin protein known to play a role in cell division, is unexpectedly and thus interestingly expressed in non-proliferating neuronal cells. There have been only a few studies reporting the neuronal functions of CCNY in synapse remodeling and hippocampal long-term potentiation. Therefore, we here provide global and comprehensive information on the putative functions of CCNY in biological and functional pathways in neuronal systems. We adopted high-throughput RNA-sequencing technology for analyzing transcriptomes regulated by CCNY and utilized bioinformatics for identifying putative molecules, biological processes, and functional pathways that are possibly connected to CCNY functions in hippocampal neuronal cells of rats. We revealed that several enriched annotation terms and pathways associated with CCNY expression within neurons, including apoptosis, learning or memory, synaptic plasticity, actin cytoskeleton, focal adhesion, extracellular matrix-receptor interaction and chemokine signaling pathway are targeted by CCNY. In addition, the mRNA levels of some genes enriched for those annotation terms and pathways or genes reported to be altered in Alzheimer’s disease mouse model were further validated by quantitative real-time PCR in hippocampal neuronal cells. The present study provides an excellent resource for future investigations of CCNY functions in neuronal systems.

细胞周期蛋白Y（Cyclin Y, CCNY）是一类已知参与细胞分裂的细胞周期蛋白，却意外且颇具研究价值地在非增殖神经元细胞中表达。目前仅有少数研究报道了CCNY在突触重塑与海马长时程增强中的神经元功能。因此，本研究旨在提供关于CCNY在神经元系统中生物学及功能通路相关潜在功能的全面系统性信息。我们采用高通量RNA测序（high-throughput RNA-sequencing）技术分析CCNY调控的转录组，并借助生物信息学方法，鉴定出大鼠海马神经元细胞中可能与CCNY功能相关的潜在分子、生物学过程及功能通路。研究发现，神经元内与CCNY表达相关的多个富集注释术语及通路均受CCNY调控，包括细胞凋亡、学习与记忆、突触可塑性、肌动蛋白细胞骨架、黏着斑、细胞外基质-受体相互作用及趋化因子信号通路等。此外，我们通过实时定量PCR（quantitative real-time PCR）在海马神经元细胞中，对富集于上述注释术语及通路的部分基因，以及阿尔茨海默病小鼠模型中报道存在表达异常的基因的mRNA水平进行了验证。本研究为未来开展神经元系统中CCNY功能的相关研究提供了优质的参考资源。