Polyamines stimulate the CHSY1 synthesis through the unfolding of the RNA G-quadruplex at the 50-untraslated region

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

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

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 50-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.

Original languageEnglish
Pages (from-to)3797-3812
Number of pages16
JournalBiochemical Journal
Volume475
Issue number23
DOIs
StatePublished - 6 Dec 2018
Externally publishedYes

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