miRNA dosage control in development and human disease

Global dosage control is an underlying miRNA regulatory strategy to achieve accurate post-transcriptional regulation.miRNA dosage control regulates embryonic development, stem cell fate decisions, neurodevelopment and immune responses.miRNA dosage control occurs at different steps of miRNA biogenesis in various physiological contexts.Dysregulation of global miRNA dosage contributes to cancer, embryo death, and neurological diseases.Artificial manipulation of global miRNA dosage provides a novel approach to treat human diseases. In mammals, miRNAs recognize target mRNAs via base pairing, which leads to a complex ‘multiple-to-multiple’ regulatory network. Previous studies have focused on the regulatory mechanisms and functions of individual miRNAs, but alterations of many individual miRNAs do not strongly disturb the miRNA regulatory network. Recent studies revealed the important roles of global miRNA dosage control events in physiological processes and pathogenesis, suggesting that miRNAs can be considered as a ‘cellular buffer’ that controls cell fate. Here, we review the current state of research on how global miRNA dosage is tightly controlled to regulate development, tumorigenesis, neurophysiology, and immunity. We propose that methods of controlling global miRNA dosage may serve as effective therapeutic tools to cure human diseases.