PABP and the poly(A) tail augment microRNA repression by facilitated miRISC binding
PABP and the poly(A) tail augment microRNA repression by facilitated miRISC binding
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DOI：
10.1038/nsmb.2309
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发表时间：
2012-06-01
影响因子：
16.8
通讯作者：
Hentze, Matthias W.
中科院分区：
文献类型：
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作者：
Moretti, Francesca;Kaiser, Constanze;Hentze, Matthias W.
多聚腺苷酸化的mRNA通常比它们的非腺苷酸化的对应物更强烈地被microRNA（miRNA）抑制。利用果蝇无细胞翻译系统，我们发现这种效应是由多聚腺苷酸结合蛋白（PABP）介导的。miRNA抑制与poly（A）尾长正相关，但当翻译被束缚的GW182沉默结构域而不是miRNA诱导的沉默复合物（miRISC）本身抑制时，这种抑制的刺激作用丧失。这些发现可以通过PABP的一个显著功能进行机械解释：它促进miRISC与miRNA调节的mRNA的关联。我们还发现，PABP与mRNA的关联随着miRISC募集和可检测到的去腺苷化之前迅速减少。我们将这些数据整合到一个修正的模型中，用于研究PABP和poly（A）尾在miRNA介导的翻译抑制中的功能。
Polyadenylated mRNAs are typically more strongly repressed by microRNAs (miRNAs) than their nonadenylated counterparts. Using a Drosophila melanogaster cell-free translation system, we found that this effect is mediated by the poly(A)-binding protein (PABP). miRNA repression was positively correlated with poly(A) tail length, but this stimulatory effect on repression was lost when translation was repressed by the tethered GW182 silencing domain rather than the miRNA-induced silencing complex (miRISC) itself. These findings are mechanistically explained by a notable function of PABP: it promotes association of miRISC with miRNA-regulated mRNAs. We also found that PABP association with mRNA rapidly diminished with miRISC recruitment and before detectable deadenylation. We integrated these data into a revised model for the function of PABP and the poly(A) tail in miRNA-mediated translational repression.