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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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1307 |
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| author | Akihiko Sakamoto Yusuke Terui Takeshi Uemura Kazuei Igarashi Keiko Kashiwagi |
| author_facet | Akihiko Sakamoto Yusuke Terui Takeshi Uemura Kazuei Igarashi Keiko Kashiwagi |
| author_sort | Akihiko Sakamoto |
| collection | DOAJ |
| 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 <i>Bmal1</i> or <i>Rev-erbα</i> 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 <i>Bmal1</i> and <i>Rev-erbα</i> were identified as the members of “polyamine modulon”, and these two proteins are significantly involved in the circadian rhythm control. |
| first_indexed | 2024-03-09T03:23:59Z |
| format | Article |
| id | doaj.art-e4af33fe94eb4ddaa90118635d6d7040 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T03:23:59Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e4af33fe94eb4ddaa90118635d6d70402023-12-03T15:05:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223130710.3390/ijms22031307Translational Regulation of Clock Genes BMAL1 and REV-ERBα by PolyaminesAkihiko Sakamoto0Yusuke Terui1Takeshi Uemura2Kazuei Igarashi3Keiko Kashiwagi4Faculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba 288-0025, JapanFaculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba 288-0025, JapanAmine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba 260-0856, JapanAmine Pharma Research Institute, Innovation Plaza at Chiba University, Chiba 260-0856, JapanFaculty of Pharmacy, Chiba Institute of Science, Choshi, Chiba 288-0025, JapanPolyamines 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 <i>Bmal1</i> or <i>Rev-erbα</i> 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 <i>Bmal1</i> and <i>Rev-erbα</i> were identified as the members of “polyamine modulon”, and these two proteins are significantly involved in the circadian rhythm control.https://www.mdpi.com/1422-0067/22/3/1307polyamine modulonBMAL1REV-ERBαcircadian clocktranslation |
| spellingShingle | Akihiko Sakamoto Yusuke Terui Takeshi Uemura Kazuei Igarashi Keiko Kashiwagi Translational Regulation of Clock Genes BMAL1 and REV-ERBα by Polyamines International Journal of Molecular Sciences polyamine modulon BMAL1 REV-ERBα circadian clock translation |
| 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 | polyamine modulon BMAL1 REV-ERBα circadian clock translation |
| url | https://www.mdpi.com/1422-0067/22/3/1307 |
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