Regulation of circadian clock by cell growth factor polyamines

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Chiba Institute of Science
• Principal Investigator: TERUI Yusuke 千葉科学大学, 薬学部, 教授 (60433687)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: ポリアミン / 概日リズム / 体内時計 / BMAL1 / 遺伝子発現制御 / 時計遺伝子 / 翻訳 / 生体分子

Outline of Final Research Achievements

We examined the relationship between polyamines and circadian rhythms.
The levels of polyamines showed a circadian rhythm. We next compared the expression level of 6 kinds of the circadian clock genes in control and DFMO (an inhibitor of polyamine synthesis) treated NIH3T3 cells. Although the mRNA level of clock genes did not alter in cells, the clock gene Bmal1 was increased about 2.5-fold at the protein level in control cells. The result suggests that Bmal1 synthesis is enhanced by polyamines at the level of translation. To clarify the mechanism of polyamine stimulation of Bmal1 synthesis, Bmal1-EGFP fusion plasmids were constructed. On the 5’-UTR of Bmal1 mRNA, there are two hairpin structures and complementary sequences to 18S rRNA necessary for ribosome shunting. Polyamine stimulation of Bmal1-EGFP synthesis disappeared by the deletion of these structures. These results suggest that polyamines enhance ribosome shunting and stimulate Bmal1 synthesis.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究により、BMAL1蛋白質のポリアミンによる合成促進機序とBMAL1の調節機構の生理的意義が明らかになり、体内時計制御の新たな経路を標的とした新規時差症候群回復薬や、様々な疾患に対する個々のリズム位相を知るための有益なバイオマーカーの開発の基盤が確立できると期待される。