Polyamines stimulate the CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 5′-untraslated region

Yamaguchi, Katsutoshi; Asakura, Kiryu; Imamura, Masataka; Kawai, Gota; Sakamoto, Taiichi; Furihata, Tomomi; Linhardt, Robert J.; Igarashi, Kazuei; Toida, Toshihiko; Higashi, Kyohei

doi:10.1042/bcj20180672

Cited by 10 publications

(10 citation statements)

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“…Although the uORF of Klf4 mRNA is 59 codons longer than MAGDIS, analysis of an uORF mutant of the reporter plasmid uORFmut did not detect translation stimulation by polyamines ( Fig 5C). Recently, it has been reported that polyamines stimulate CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 5 0 -untrasnslated region [41]. A similar 12-nucleotide guanine quartet (CGG) 4 motif that can form RNA G-quadruplex structures is also present in the 5 0 -UTR of Klf4 mRNA.…”

Section: Discussionmentioning

confidence: 99%

KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation

et al. 2020

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Mast cells have secretory granules containing chemical mediators such as histamine and play important roles in the immune system. Polyamines are essential factors for cellular processes such as gene expression and translation. It has been reported that secretory granules contain both histamine and polyamines, which have similar chemical structures and are produced from the metabolism of cationic amino acids. We investigated the effect of polyamine depletion on mast cells using bone marrow-derived mast cells (BMMCs). Polyamine depletion was induced using α-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase. DFMO treatment resulted in a significant reduction of cell number and abnormal secretory granules in BMMCs. Moreover, the cells showed a 2.3-fold increase in intracellular histamine and up-regulation of histidine decarboxylase (HDC) at the transcriptional level during BMMC differentiation. Levels of the transcription factor kruppel-like factor 4 (KLF4) greatly decreased upon DFMO treatment; however, Klf4 mRNA was expressed at levels similar to controls. We determined the translational regulation of KLF4 using reporter genes encoding Klf4-luc2 fusion mRNA, for transfecting NIH3T3 cells, and performed in vitro translation. We found that the efficiency of KLF4 synthesis in response to DFMO treatment was enhanced by the existence of a GC-rich 5 0 -untranslated region (5 0 -UTR) on Klf4 mRNA, regardless of the recognition of the initiation codon. Taken together, these results indicate that the enhancement of histamine synthesis by DFMO depends on the up-regulation of Hdc expression, achieved by removal of transcriptional suppression of KLF4, during differentiation. OPEN ACCESS Citation: Nishimura K, Okamoto M, Shibue R, Mizuta T, Shibayama T, Yoshino T, et al. (2020) KLF4 is required for suppression of histamine synthesis by polyamines during bone marrowderived mast cell differentiation. PLoS ONE 15(2): e0229744. https://doi.

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Section: Discussionmentioning

confidence: 99%

KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation

et al. 2020

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“…observed in polyamine-depleted cells (Fig. 4) (11). Because molecular weight (Mw) of CS in HCT116 cells was also reduced by polyamine depletion (not shown), we explored the genes whose expression level is enhanced by polyamines in CS biosynthetic pathway, especially polymerization and 4-O-sulfation of CS.…”

Section: E173mentioning

confidence: 99%

“…mRNA and of G4 formation in CHSY1 mRNA by polyamines result in the enhancement of the syntheses of EXT2 and CHSY1 (10,11). Because intracellular polyamine levels are also strictly and quickly regulated by biosynthesis, degradation and transport ).…”

Section: E the Physiological Role Of Translational Regulation By Polmentioning

confidence: 99%

“…The distribution and number of protein-binding sites containing IdoA and di-sulfated disaccharides in the GAG chains are also important for the interaction with the GAG-binding proteins including ATIII or receptor-type protein tyrosine phosphatase PTPRσ (2,6). Therefore, GAG biosynthesis by glycosyltransferases, sulfotransferases, and C5 epimerase is intricately regulated at multiple levels in mammals as the degree of sulfation and GAG C5 epimerization are both tissue-and cell type-specific (7)(8)(9)(10)(11). There are several reports describing that the ratio of the 4-O-sulfation and 6-Osulfation (4S/6S) in CS disaccharides, changed during the normal embryonic development, growth, and aging (12)(13)(14)(15)(16).…”

Section: A Introductionmentioning

confidence: 99%

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Expression of Glycosaminoglycan-Related Genes and the Role of Polyamines in the Glycosaminoglycan Biosynthetic Pathways

Higashi

2020

TIGG

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Glycosaminoglycans (GAGs), a group of structurally related acidic polysaccharides, are primarily present as glycan moieties of proteoglycans (PGs). The physiological functions of PGs depend on the interaction between the glycan moieties and proteins such as growth factors, chemokines, and adhesion molecules. For this reason, the sulfation pattern, the degree of epimerization, and the glycan moiety chain length impact their interactions with GAG-binding proteins. Although the structural changes in GAGs occur during the development and aging process, their detailed mechanisms are not fully understood. This review provides an overview of the heparan sulfate (HS)-and chondroitin sulfate (CS)-related gene expression at the transcriptional and translational level. In addition, it also describes the molecular mechanisms of the polyamine stimulation of glycosaminoglycan synthesis. HS biosynthesis was initiated once N-acetylglucosamine (GlcNAc) is transferred by EXTL3 to the common linkage tetrasaccharides, glucuronic acid (GlcA)β1-3galactose (Gal)β1-3Galβ1-4-xylose (Xyl)β1-O-Ser in PGs (19). Chain elongation is catalyzed by the EXT1/EXT2 heterodimer through the alternate addition of GlcNAc and GlcA residues (19). If GlcNAc is transferred to the linkage region by EXTL2, initiation of chain elongation is inhibited. HS backbone is epimerized and sulfated by

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“…In mammalian cells, to identify members of the polyamine modulon, polyamine-reduced cells were prepared using a-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, and proteins in cells were compared between control and polyamine-reduced cells. Seven proteins stimulated by polyamines thus far identified were Cct2, Hnrpl, and Pgam1 (12), eEF1A (13), p16 (7), EXT2 (14) and CHSY1 (15). The mechanisms of polyamine stimulation are as follows.…”

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Polyamines regulate gene expression by stimulating translation of histone acetyltransferase mRNAs

Sakamoto

Terui

Uemura

et al. 2020

Journal of Biological Chemistry

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Polyamines regulate gene expression in Escherichia coli by translationally stimulating mRNAs encoding global transcription factors. In this study, we focused on histone acetylation, one of the mechanisms of epigenetic regulation of gene expression, to attempt to clarify the role of polyamines in the regulation of gene expression in eukaryotes. We found that activities of histone acetyltransferases in both the nucleus and cytoplasm decreased significantly in polyamine-reduced mouse mammary carcinoma FM3A cells. Although protein levels of histones H3 and H4 did not change in control and polyamine-reduced cells, acetylation of histones H3 and H4 was greatly decreased in the polyamine-reduced cells. Next, we used control and polyamine-reduced cells to identify histone acetyltransferases whose synthesis is stimulated by polyamines. We found that polyamines stimulate the translation of histone acetyltransferases GCN5 and HAT1. Accordingly, GCN5- and HAT1-catalyzed acetylation of specific lysine residues on histones H3 and H4 was stimulated by polyamines. Consistent with these findings, transcription of genes required for cell proliferation was enhanced by polyamines. These results indicate that polyamines regulate gene expression by enhancing the expression of the histone acetyltransferases GCN5 and HAT1 at the level of translation. Mechanistically, polyamines enhanced the interaction of microRNA-7648-5p (miR-7648-5p) with the 5′-UTR of GCN5 mRNA, resulting in stimulation of translation due to the destabilization of the double-stranded RNA (dsRNA) between the 5′-UTR and the ORF of GCN5 mRNA. Because HAT1 mRNA has a short 5′-UTR, polyamines may enhance initiation complex formation directly on this mRNA.

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Polyamines stimulate the CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 5′-untraslated region

Cited by 10 publications

References 52 publications

KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation

KLF4 is required for suppression of histamine synthesis by polyamines during bone marrow-derived mast cell differentiation

Expression of Glycosaminoglycan-Related Genes and the Role of Polyamines in the Glycosaminoglycan Biosynthetic Pathways

Polyamines regulate gene expression by stimulating translation of histone acetyltransferase mRNAs

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