Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.

Polyamines release the let-7b-mediated suppression of initiation codon recognition during the protein synthesis of EXT2.
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DOI:
10.1038/srep33549
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发表时间:
2016-09-21
期刊:
影响因子:
4.6
通讯作者:
Toida T
Toida T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
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

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蛋白聚糖(Proteoglycans,PGs)是一类糖胺聚糖(glycosaminoglycan,GAG)-蛋白质糖复合物,通过其糖链与生长因子、趋化因子和粘附分子的相互作用参与动物的生理功能。然而,尚不清楚GAG结构在老化过程中如何变化。在这里,我们发现,多胺水平与硫酸乙酰肝素(HS)在人体皮肤中的表达水平相关。在培养的细胞系中,启动HS生物合成的EXT1和EXT2酶在翻译水平上被多胺刺激。有趣的是,在EXT2翻译过程中43S前起始复合物的起始密码子识别被let-7 microRNA家族的成员let-7b抑制,通过结合EXT2 mRNA的N-末端氨基酸编码序列。Let-7b对起始密码子的抑制依赖于EXT2 mRNA的5 ′-UTR长度,多胺可抑制Let-7b对起始密码子的抑制作用。这些发现为研究与miRNA和多胺相关的HS生物合成提供了新的见解。
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.
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