title: Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.
abstract: Proteoglycans (PGs), a family of glycosaminoglycan (GAG)-protein glycoconjugates, contribute to animal physiology through interactions between their glycan chains and growth factors, chemokines and adhesion molecules. However, it remains unclear how GAG structures are changed during the aging process. Here, we found that polyamine levels are correlated with the expression level of heparan sulfate (HS) in human skin. In cultured cell lines, the EXT1 and EXT2 enzymes, initiating HS biosynthesis, were stimulated at the translational level by polyamines. Interestingly, the initiation codon recognition by 43S preinitiation complex during EXT2 translation is suppressed by let-7b, a member of the let-7 microRNA family, through binding at the N-terminal amino acid coding sequence in EXT2 mRNA. Let-7b-mediated suppression of initiation codon depends on the length of 5'-UTR of EXT2 mRNA and its suppression is inhibited in the presence of polyamines. These findings provide new insights into the HS biosynthesis related to miRNA and polyamines.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Imamura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Higashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kiryu
authors.initials: K
authors.lastname: Asakura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Furihata
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Terui
authors.affiliation: Department of Plastic and Reconstructive Surgery, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Satake
authors.affiliation: Department of Plastic and Reconstructive Surgery, Yokohama City University Hospital, 3-9 Fukuura Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Maegawa
authors.affiliation: Department of Plastic and Reconstructive Surgery, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yasumura
authors.affiliation: Department of Biological Science and Nursing, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Ibuki
authors.affiliation: Department of Biological Science and Nursing, Graduate School of Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Akase
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishimura
authors.affiliation: Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kashiwagi
authors.affiliation: Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th Street Troy, NY 12180, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Linhardt
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.|Amine Pharma Research Institute, Innovation Plaza at Chiba University, 1-8-15 Inohana, Chuo-ku, Chiba 260-0856, Japan.
authors.forename: Kazuei
authors.initials: K
authors.lastname: Igarashi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Toida
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018387:Codon, Initiator; D004187:Disaccharides / Q000378:metabolism; D000518:Eflornithine / Q000494:pharmacology; D006497:Heparan Sulfate; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D017351:N-Acetylglucosaminyltransferases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D011073:Polyamines / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects; D000099065:Exostosin 2; D000099058:Exostosin 1
chemical_list: D020121:5' Untranslated Regions; D018387:Codon, Initiator; D004187:Disaccharides; D000518:Eflornithine; D006497:Heparan Sulfate; D035683:MicroRNAs; D017351:N-Acetylglucosaminyltransferases; D011073:Polyamines; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; D000099065:Exostosin 2; D000099058:Exostosin 1; C542687:mirnlet7 microRNA, mouse