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

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...

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Autores principales: Sakamoto, Akihiko, Terui, Yusuke, Uemura, Takeshi, Igarashi, Kazuei, Kashiwagi, Keiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865260/
https://www.ncbi.nlm.nih.gov/pubmed/33525630
http://dx.doi.org/10.3390/ijms22031307
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author Sakamoto, Akihiko
Terui, Yusuke
Uemura, Takeshi
Igarashi, Kazuei
Kashiwagi, Keiko
author_facet Sakamoto, Akihiko
Terui, Yusuke
Uemura, Takeshi
Igarashi, Kazuei
Kashiwagi, Keiko
author_sort Sakamoto, Akihiko
collection PubMed
description 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.
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spelling pubmed-78652602021-02-07 Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines Sakamoto, Akihiko Terui, Yusuke Uemura, Takeshi Igarashi, Kazuei Kashiwagi, Keiko Int J Mol Sci Article 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. MDPI 2021-01-28 /pmc/articles/PMC7865260/ /pubmed/33525630 http://dx.doi.org/10.3390/ijms22031307 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sakamoto, Akihiko
Terui, Yusuke
Uemura, Takeshi
Igarashi, Kazuei
Kashiwagi, Keiko
Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines
title Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines
title_full Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines
title_fullStr Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines
title_full_unstemmed Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines
title_short Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines
title_sort translational regulation of clock genes bmal1 and rev-erbα by polyamines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865260/
https://www.ncbi.nlm.nih.gov/pubmed/33525630
http://dx.doi.org/10.3390/ijms22031307
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