Abstract

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.

Highlights

  • Cyclin Y (CCNY) is one of the members of the cyclin family that has been known to regulate cell division in proliferating cells [1,2,3]

  • We first searched for systematic information of gene sets that are possibly regulated by CCNY in the hippocampal neurons; the region of hippocampus was chosen based on the previous report on the function of CCNY in hippocampal long-term potentiation (LTP) [11]

  • For the first time, we demonstrated the expression patterns of transcripts targeted by the cyclin protein CCNY in non-proliferating hippocampal neuronal cells

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Summary

Introduction

Cyclin Y (CCNY) is one of the members of the cyclin family that has been known to regulate cell division in proliferating cells [1,2,3]. CCNY was originally identified as an interacting protein of the cyclin-dependent kinase CDK14/PFTK1 via a yeast two-hybrid screen [4]. Its role has been investigated in the field of cancer biology by showing that CCNY regulates glioma. Cyclin Y-mediated transcriptome analysis in hippocampal neurons and lung cancer cell proliferation [5, 6]. CCNY played an essential role in the maintenance of mammary stem/progenitor cell properties [7] and the control of adipogenesis and lipid production [8]. CCNY was a key factor for the development of Drosophila, including larval growth, pupal development and metamorphosis [2]

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