CPEB2, CPEB3 and CPEB4 are coordinately regulated by miRNAs recognizing conserved binding sites in paralog positions of their 3'-UTRs.
CPEB2, CPEB3 and CPEB4 are coordinately regulated by miRNAs recognizing conserved binding sites in paralog positions of their 3'-UTRs.
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DOI：
10.1093/nar/gkq635
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发表时间：
2010-11
影响因子：
14.9
通讯作者：
Muro AF
中科院分区：
文献类型：
--
作者：
Morgan M;Iaconcig A;Muro AF
胞质多聚腺苷酸化元件结合蛋白（CPEB）是一种参与翻译调控的RNA结合蛋白。CPEB 2、CPEB 3和CPEB 4是它们之间非常相似的parabolic蛋白，称为CPEB 2亚家族。为了深入了解CPEB 2亚家族转录物的共同调控机制，我们寻找了三种旁系同源物3′-UTR中存在的假定顺式作用元件。我们发现了不同家族的miRNAs预测靶向所有亚家族成员。这些家族的大多数预测的靶位点位于parabolic位置，这表明这些推定的调控基序已经存在于祖先基因中。我们使用报告构建体中的miRNA结合位点的诱变结合miRNA的过表达和缺失来验证三种旁系同源物中miR-92和miR-26的靶位点。miR-92和miR-26均诱导荧光素酶活性降低，这与报告基因构建体的mRNA水平降低相关。我们还发现，内源性miRNA共调节CPEB 2，CPEB 3和CPEB 4转录，支持我们的假设，这些基因有一个共同的调控机制介导的miRNA。我们还认为，在每个3′-UTR中高度保守的元件的产生过程中，miRNA结合基序的祖先模式得以保持。
The cytoplasmic polyadenylation element binding-protein (CPEB) is an RNA-binding protein that participates in translational control. CPEB2, CPEB3 and CPEB4 are paralog proteins very similar among themselves referred as the CPEB2 subfamily. To gain insight into common mechanisms of regulation of the CPEB2 subfamily transcripts, we looked for putative cis-acting elements present in the 3′-UTRs of the three paralogs. We found different families of miRNAs predicted to target all subfamily members. Most predicted target sites for these families are located in paralog positions suggesting that these putative regulatory motifs were already present in the ancestral gene. We validated target sites for miR-92 and miR-26 in the three paralogs using mutagenesis of miRNA-binding sites in reporter constructs combined with over-expression and depletion of miRNAs. Both miR-92 and miR-26 induced a decrease in Luciferase activity associated to a reduction in mRNA levels of the reporter constructs. We also showed that the endogenous miRNAs co-regulate CPEB2, CPEB3 and CPEB4 transcripts, supporting our hypothesis that these genes have a common regulatory mechanism mediated by miRNAs. We also suggest that the ancestral pattern of miRNA-binding motifs was maintained throughout the generation of highly conserved elements in each of the 3′-UTRs.
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影响因子：
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