Transforming growth factor-beta(1) stimulates multiple protein interactions at a unique cis-element in the 3'-untranslated region of the hyaluronan receptor RHAMM mRNA
Transforming growth factor-beta(1) stimulates multiple protein interactions at a unique cis-element in the 3'-untranslated region of the hyaluronan receptor RHAMM mRNA
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DOI：
10.1074/jbc.271.25.15279
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发表时间：
1996-06-21
影响因子：
4.8
通讯作者：
Wright, JA
中科院分区：
文献类型：
--
作者：
Amara, FM;Entwistle, J;Wright, JA
透明质酸介导的运动受体（RHAMMM）基因表达在暴露于转化生长因子- β (tgf - β(1))的纤维肉瘤中显著升高，在tgf - β处理的细胞中，RHAMM mRNA的半衰期增加了3倍(1)，表明生长因子对RHAMM基因表达的调节至少部分涉及转录后机制。我们的研究表明，一个独特的30个核苷酸（nt）区域具有3个拷贝的序列，GCU-UGC，是介导信息稳定性的3'-非翻译区（3'-UTR）中的tgf - β(1)应答区，该区域特异性地与细胞质反式因子相互作用，在tgf - β(1)处理后形成约175、97、63、26和17 kDa的多个蛋白复合物，表明这些复合物在tgf - β(1)诱导的信息稳定的作用机制中起作用。在稳定转染的细胞中，将3'-UTR插入氯霉素乙酰转移酶基因赋予tgf - β(1)诱导的氯霉素乙酰转移酶杂交RNA的稳定性，而同样的插入包含30-nt区域的缺失对mRNA的稳定性没有显著影响。这些结果提供了一个RHAMM信息调控的模型，其中tgf - β(1)介导的RHAMM信息稳定性的改变涉及上调与3'-UTR中30-nt顺式元件稳定性决定因素的多种蛋白质相互作用，该模型还表明该30-nt碱基区域顺式作用于静息正常细胞中RHAMM mRNA的不稳定。
The receptor for hyaluronan mediated motility (RHAMMM) gene expression is markedly elevated in fibrosarcomas exposed to transforming growth factor-beta(1) (TGF-beta(1)), The half-life of RHAMM mRNA was increased by 3 fold in cells treated with TGF-beta(1), indicating that growth factor regulation of RHAMM gene expression at least in part involves a posttranscriptional mechanism, Our studies demonstrated that a unique 30-nucleotide (nt) region that has three copies of the sequence, GCU-UGC, was the TGF-beta(1)-responsive region in the 3'-untranslated region (3'-UTR) that mediated message stability, This region interacted specifically with cytoplasmic trans-factors to form multiple protein com plexes of approximately 175, 97, 63, 26, and 17 kDa post-TGF-beta(1) treatment, suggesting a role for these complexes in the mechanism of action of TGF-beta(1)-induced message stabilization, Insertion of the 3'-UTR into the chloramphenicol acetyltransferase gene conferred TGF-beta(1) induced stability of chloramphenicol acetyltransferase-hybrid RNA in stably transfected cells, while the same insert carrying a deletion containing the 30-nt region had no significant effect on mRNA stability, These results provide a model of RHAMM message regulation in which TGF-beta(1)-mediated alteration of RHAMM message stability involves the up-regulation of multiple protein interactions with a 30-nt cis-element stability determinant in the 3'-UTR, This model also suggests that this 30-nt base region functions in cis to destabilize RHAMM mRNA in resting normal cells.