Target repression induced by endogenous microRNAs: large differences, small effects.
Target repression induced by endogenous microRNAs: large differences, small effects.
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DOI：
10.1371/journal.pone.0104286
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ronshaugen M
中科院分区：
文献类型：
--
作者：
Kozomara A;Hunt S;Ninova M;Griffiths-Jones S;Ronshaugen M
MicroRNAs是调节蛋白质水平的小rna。通常认为microRNA的表达水平与其抑制活性直接相关，即高表达的microRNA会更多地抑制其靶mrna。本文研究了黑腹果蝇S2细胞中32种成熟microRNA的内源性表达与抑制之间的定量关系。总的来说，我们发现更丰富的microrna对其靶标的抑制程度更大。然而，表达和抑制之间的关系是非线性的，因此10倍的microRNA浓度只会增加10%的目标抑制。显性引导microRNA和次要成熟产物（所谓的乘客链/microRNA*序列）的表达/抑制关系是相同的。然而，我们发现了microrna的例子，其细胞浓度相差几个数量级，但诱导类似的靶mrna抑制。同样，具有相似表达的microrna可能具有非常不同的抑制能力。我们表明，microrna与Argonaute蛋白的关联并不能解释这种抑制的变化。观察到的关系与目标抑制的限制性步骤是microRNA/RISC复合物与目标位点的关联是一致的。这些发现表明，细胞microRNA浓度的适度变化将对抑制靶标产生轻微影响。
MicroRNAs are small RNAs that regulate protein levels. It is commonly assumed that the expression level of a microRNA is directly correlated with its repressive activity – that is, highly expressed microRNAs will repress their target mRNAs more. Here we investigate the quantitative relationship between endogenous microRNA expression and repression for 32 mature microRNAs in Drosophila melanogaster S2 cells. In general, we find that more abundant microRNAs repress their targets to a greater degree. However, the relationship between expression and repression is nonlinear, such that a 10-fold greater microRNA concentration produces only a 10% increase in target repression. The expression/repression relationship is the same for both dominant guide microRNAs and minor mature products (so-called passenger strands/microRNA* sequences). However, we find examples of microRNAs whose cellular concentrations differ by several orders of magnitude, yet induce similar repression of target mRNAs. Likewise, microRNAs with similar expression can have very different repressive abilities. We show that the association of microRNAs with Argonaute proteins does not explain this variation in repression. The observed relationship is consistent with the limiting step in target repression being the association of the microRNA/RISC complex with the target site. These findings argue that modest changes in cellular microRNA concentration will have minor effects on repression of targets.
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