Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines.

Akihiko Sakamoto,Yusuke Terui,Takeshi Uemura,Kazuei Igarashi,Keiko Kashiwagi

doi:10.3390/ijms22031307

Abstract

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 Bmal1 or Rev-erbα 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 Bmal1 and Rev-erbα were identified as the members of “polyamine modulon”, and these two proteins are significantly involved in the circadian rhythm control.

Highlights

Polyamines are cationic aliphatic amines present in almost all living organisms [1,2]
The results support some reports that polyamines are regulated by circadian clock genes and suggest that polyamines regulate the expression of clock genes and functions [16]
To elucidate the role of polyamines in the circadian clock at the molecular level, we looked for clock genes whose synthesis is stimulated by polyamines

Summary

Introduction

Polyamines (putrescine, spermidine, and spermine) are cationic aliphatic amines present in almost all living organisms [1,2]. Fifth, when a microRNA stimulates protein synthesis, polyamines enhance the interaction between the 5 -UTR of mRNA with the microRNA, resulting in the destabilization of the double-stranded RNA between the 5 -UTR and the open reading frame (ORF) of mRNA. This was observed in GCN5 (histone acetyltransferase in the nuclei) synthesis [10]. Sixth, when the size of 5 -UTR is short, initiation complex formation (AUGdependent Met-tRNAi binding to 80S ribosomes) is stimulated by polyamines This was observed in HAT1 (histone acetyltransferase in cytoplasm) synthesis [10]

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Results

Conclusion