Glycosaminoglycans (GAGs), a group of structurally related acidic polysaccharides, are primarily found as glycan moieties of proteoglycans (PGs). Among these, chondroitin sulfate (CS) and dermatan sulfate, side chains of PGs, are widely distributed in animal kingdom and show structural variations, such as sulfation patterns and degree of epimerization, which are responsible for their physiological functions through interactions with growth factors, chemokines and adhesion molecules. However, structural changes in CS, particularly the ratio of 4-O-sulfation to 6-O-sulfation (4S/6S) and CS chain length that occur during the aging process, are not fully understood. We found that 4S/6S ratio and molecular weight of CS were decreased in polyamine-depleted cells. In addition, decreased levels of chondroitin synthase 1 (CHSY1) and chondroitin 4-O-sulfotransferase 2 proteins were also observed on polyamine depletion. Interestingly, the translation initiation of CHSY1 was suppressed by a highly structured sequence (positions −202 to −117 relative to the initiation codon) containing RNA G-quadruplex (G4) structures in 5′-untranslated region. The formation of the G4s was influenced by the neighboring sequences to the G4s and polyamine stimulation of CHSY1 synthesis disappeared when the formation of the G4s was inhibited by site-directed mutagenesis. These results suggest that the destabilization of G4 structures by polyamines stimulates CHSY1 synthesis and, at least in part, contribute to the maturation of CS chains.
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December 2018
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The cover image represents the scheme of DNA-linked inhibitor antibody assay (DIANA) as a new method for screening influenza neuraminidase inhibitors, described in this issue by Kožíšek et al. For further details, see pages 3847–3860.
Research Article|
December 06 2018
Polyamines stimulate the CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 5′-untraslated region
Katsutoshi Yamaguchi;
Katsutoshi Yamaguchi
*
1Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Kiryu Asakura;
Kiryu Asakura
*
1Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Masataka Imamura;
Masataka Imamura
1Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Gota Kawai;
Gota Kawai
2Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan
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Taiichi Sakamoto;
Taiichi Sakamoto
2Department of Life and Environmental Sciences, Chiba Institute of Technology, 2-17-1 Tsudanuma, Narashino, Chiba 275-0016, Japan
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Tomomi Furihata;
Tomomi Furihata
1Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Robert J. Linhardt;
Robert J. Linhardt
3Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street, Troy, NY 12180, U.S.A.
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Kazuei Igarashi;
Kazuei Igarashi
1Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
4Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan
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Toshihiko Toida;
Toshihiko Toida
1Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
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Kyohei Higashi
1Department of Clinical and Analytical Biochemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan
5Department of Clinical and Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Correspondence: Kyohei Higashi (higase@rs.tus.ac.jp)
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Publisher: Portland Press Ltd
Received:
August 16 2018
Revision Received:
October 04 2018
Accepted:
November 05 2018
Accepted Manuscript online:
November 06 2018
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem J (2018) 475 (23): 3797–3812.
Article history
Received:
August 16 2018
Revision Received:
October 04 2018
Accepted:
November 05 2018
Accepted Manuscript online:
November 06 2018
Citation
Katsutoshi Yamaguchi, Kiryu Asakura, Masataka Imamura, Gota Kawai, Taiichi Sakamoto, Tomomi Furihata, Robert J. Linhardt, Kazuei Igarashi, Toshihiko Toida, Kyohei Higashi; Polyamines stimulate the CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 5′-untraslated region. Biochem J 12 December 2018; 475 (23): 3797–3812. doi: https://doi.org/10.1042/BCJ20180672
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