RRC ID 51870
Author Imamura M, Higashi K, Yamaguchi K, Asakura K, Furihata T, Terui Y, Satake T, Maegawa J, Yasumura K, Ibuki A, Akase T, Nishimura K, Kashiwagi K, Linhardt RJ, Igarashi K, Toida T.
Title Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.
Journal Sci Rep
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.
Volume 6
Pages 33549
Published 2016-9-21
DOI 10.1038/srep33549
PII srep33549
PMID 27650265
PMC PMC5030709
MeSH 5' Untranslated Regions / genetics Adult Aged Amino Acid Sequence Animals Base Sequence Binding Sites Codon, Initiator* Disaccharides / metabolism Eflornithine / pharmacology Heparitin Sulfate Humans Mice MicroRNAs / metabolism* Middle Aged N-Acetylglucosaminyltransferases / biosynthesis* N-Acetylglucosaminyltransferases / chemistry N-Acetylglucosaminyltransferases / genetics N-Acetylglucosaminyltransferases / metabolism NIH 3T3 Cells Polyamines / pharmacology* Protein Biosynthesis* / drug effects RNA, Messenger / genetics RNA, Messenger / metabolism RNA-Induced Silencing Complex / metabolism Skin / drug effects Skin / pathology Wound Healing / drug effects
IF 4.011
Human and Animal Cells ATDC5(RCB0565)