RNA interference (RNAi)/miRNA has been recognized as one of the most important regulation mechanisms of gene expression at post-transcriptional? levels in eukaryotic cells. Although the main components within the RNAi/miRNA pathway have been identified and characterized, studies on the molecular mechanisms regulating the activity of the RNAi/miRNA pathway have begun to emerge in recent years. High-throughput reporter assays have been developed to monitor the activity of the RNAi/miRNA pathway and applied for proof-of-concept pilot screening, leading to identification of some inhibitors and activators that generally or specifically regulate activity of the RNAi/ miRNA pathway. Additionally, in combination with multidisciplinary approaches such as proteomics, biochemistry and genetics, to identify the targeting components, some protein co-factors that play significant roles in the regulation of the activity of the RNAi/miRNA pathway have been identified. Herein we highlight the high throughput reporter assays developed in recent years and the resulting discovery of the RNAi/miRNA enhancers and inhibitors, with attention on developing novel RNAi- or miRNA-based therapeutic interventions.

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