Knockout of the ubiquitously expressed miRNA-17∼92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17∼92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17∼92:Bim interactions to the complex miR-17∼92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17∼92 seed matches. Blocking miR-17∼92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17∼92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17∼92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts.

中文翻译：

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通过 miRNA 控制的 BIM 变阻器对细胞存活的上下文特定调节。

在小鼠中敲除普遍表达的 miRNA-17∼92 簇会导致致命的发育性肺缺陷、骨骼异常和 B 淋巴细胞生成受阻。miR-17∼92 miRNA 的共同目标是促凋亡蛋白 BIM，它是哺乳动物细胞生死决定的核心。为了阐明 miR-17∼92:Bim 相互作用对复杂的 miR-17∼92 敲除表型的贡献，我们使用了九个 Bim 3' UTR miR-17∼92 种子匹配的条件诱变系统。在发育早期阻断 miR-17∼92:Bim 相互作用表型复制了 miR-17∼92 消融的致命肺表型，并产生了骨骼卷曲的尾巴。在造血系统中，它并没有引起预测的 B 细胞发育阻滞，而是导致 B 细胞选择性地无法抵抗细胞应激；并防止由 Bim 单倍体不足引起的 B 和 T 细胞增生。因此，miR-17∼92 与单个靶标的相互作用对生命至关重要，miRNA 对 BIM 的调节可作为特定生理环境中控制细胞存活的变阻器。