Each microRNA (miRNA) represses a web of target genes and, through them, controls multiple phenotypes. The difficulties inherent in such controls cast doubt on how effective miRNAs are in driving phenotypic changes. A “simple regulation” model posits “one target–one phenotype” control under which most targeting is nonfunctional. In an alternative “coordinate regulation” model, multiple targets are assumed to control the same phenotypes coherently, and most targeting is functional. Both models have some empirical support but pose different conceptual challenges. Here, we concurrently analyze multiple targets and phenotypes associated with the miRNA-310 family (miR310s) of Drosophila. Phenotypic rescue in the mir310s knockout background is achieved by promoter-directed RNA interference that restores wild-type expression. For one phenotype (eggshell morphology), we observed redundant regulation, hence rejecting “simple regulation” in favor of the “coordinate regulation” model. For other phenotypes (egg-hatching and male fertility), however, one gene shows full rescue, but three other rescues aggravate the phenotype. Overall, phenotypic controls by miR310s do not support either model. Like a thermostat that controls both heating and cooling elements to regulate temperature, redundancy and incoherence in regulation generally suggest some capacity in stability control. Our results therefore support the published view that miRNAs play a role in the canalization of transcriptome and, hence, phenotypes.

每个microRNA（miRNA）都可抑制目标基因的网络，并通过它们控制多种表型。这种控制方法固有的困难使人们怀疑miRNA在驱动表型变化方面有多有效。“简单调节”模型假定“一个目标一表型”控制，在该控制下大多数目标是无功能的。在替代的“坐标调节”模型中，假定多个目标可以连贯地控制相同的表型，并且大多数目标是有效的。两种模型都有一定的经验支持，但提出了不同的概念挑战。在这里，我们同时分析与果蝇的miRNA-310家族（miR310s）相关的多个靶标和表型。mir310s中的表型抢救通过恢复野生型表达的启动子指导的RNA干扰获得基因敲除背景。对于一种表型（卵壳形态），我们观察到多余的调控，因此拒绝了“简单调控”，而倾向于“坐标调控”模型。然而，对于其他表型（卵孵化和雄性育性），一个基因显示出完全的拯救，而其他三个拯救则加剧了该表型。总体而言，miR310的表型对照不支持任何一种模型。就像可以同时控制加热和冷却元件以调节温度的恒温器一样，调节中的冗余和不连贯性通常暗示了稳定性控制的能力。因此，我们的研究结果支持了已发表的观点，即miRNA在转录组的通道化以及表型的通道化中起作用。