Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation
Competitive binding of AUF1 and TIAR to MYC mRNA controls its translation
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DOI：
10.1038/nsmb1249
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发表时间：
2007-06-01
影响因子：
16.8
通讯作者：
Brewer, Gary
中科院分区：
文献类型：
--
作者：
Liao, Baisong;Hu, Yan;Brewer, Gary
3个非翻译区中的富含（A+U）的元件（战神）是编码许多癌蛋白和细胞因子的信使RNA快速降解的信号。ARE结合蛋白AUF 1有助于它们的降解。我们确定MYC原癌基因mRNA作为细胞AUF1靶点。MYC翻译和细胞增殖的水平与AUF1丰度成正比，但与ARE结合蛋白TIAR（MYC翻译抑制因子）的丰度成反比。AUF1和TIAR均通过ARE影响MYC翻译，而不影响mRNA丰度。在体内改变一种ARE结合蛋白与MYC mRNA的结合会影响mRNA与另一种蛋白的结合。最后，遗传实验表明，AUF1和TIAR通过MYC依赖性途径控制增殖。总之，这些观察结果表明了一种新的调节机制，其中调节与MYC mRNA结合的AUF1和TIAR的比率允许动态控制MYC翻译和细胞增殖。
(A+U)-rich elements (AREs) within 3 untranslated regions are signals for rapid degradation of messenger RNAs encoding many oncoproteins and cytokines. The ARE-binding protein AUF1 contributes to their degradation. We identified MYC proto-oncogene mRNA as a cellular AUF1 target. Levels of MYC translation and cell proliferation were proportional to AUF1 abundance but inversely proportional to the abundance of the ARE-binding protein TIAR, a MYC translational suppressor. Both AUF1 and TIAR affected MYC translation via the ARE without affecting mRNA abundance. Altering association of one ARE-binding protein with MYC mRNA in vivo reciprocally affected mRNA association with the other protein. Finally, genetic experiments revealed that AUF1 and TIAR control proliferation by a MYC-dependent pathway. Together, these observations suggest a novel regulatory mechanism where tuning the ratios of AUF1 and TIAR bound to MYC mRNA permits dynamic control of MYC translation and cell proliferation.