Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba 288-0025, Japan.
Amine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba 260-0856, Japan.
Int J Mol Sci. 2021 Jan 28;22(3):1307. doi: 10.3390/ijms22031307.
Polyamines stimulate the synthesis of specific proteins at the level of translation, and the genes encoding these proteins are termed as the "polyamine modulon". The circadian clock generates daily rhythms in mammalian physiology and behavior. We investigated the role of polyamines in the circadian rhythm using control and polyamine-reduced NIH3T3 cells. The intracellular polyamines exhibited a rhythm with a period of about 24 h. In the polyamine-reduced NIH3T3 cells, the circadian period of circadian clock genes was lengthened and the synthesis of BMAL1 and REV-ERBα was significantly reduced at the translation level. Thus, the mechanism of polyamine stimulation of these protein syntheses was analyzed using NIH3T3 cells transiently transfected with genes encoding enhanced green fluorescent protein (EGFP) fusion mRNA with normal or mutated 5'-untranslated region (5'-UTR) of or mRNA. It was found that polyamines stimulated BMAL1 and REV-ERBα synthesis through the enhancement of ribosomal shunting during the ribosome shunting within the 5'-UTR of mRNAs. Accordingly, the genes encoding and were identified as the members of "polyamine modulon", and these two proteins are significantly involved in the circadian rhythm control.
多胺在翻译水平上刺激特定蛋白质的合成，编码这些蛋白质的基因被称为“多胺调控模块”。生物钟在哺乳动物的生理和行为中产生每日节律。我们使用对照和多胺减少的 NIH3T3 细胞研究了多胺在生物钟节律中的作用。细胞内多胺表现出约 24 小时的节律。在多胺减少的 NIH3T3 细胞中，生物钟基因的昼夜节律周期延长，BMAL1 和 REV-ERBα 的翻译水平显著降低。因此，使用瞬时转染编码增强型绿色荧光蛋白（EGFP）融合 mRNA 的 NIH3T3 细胞分析了多胺刺激这些蛋白质合成的机制，该 mRNA 的 5'-UTR 具有正常或突变的 5'-UTR。结果发现，多胺通过在 mRNA 的 5'-UTR 内核糖体移位期间增强核糖体移位来刺激 BMAL1 和 REV-ERBα 的合成。因此，编码 和 的基因被鉴定为“多胺调控模块”的成员，这两种蛋白质都显著参与生物钟节律控制。
