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Many proteins are expressed dynamically during different stages of cellular life and the accuracy of protein amounts is critical for cell endurance. Therefore, cells should have a perceptive system that notifies about fluctuations in the amounts of certain components and an executive system that efficiently restores their precise levels. At least one mechanism that evolution has employed for this task is regulation of 3′-UTR length for microRNA targeting. Here we show that in Drosophila the microRNA complex miR-310s acts as an executive mechanism to buffer levels of the muscular dystrophy-associated extracellular matrix receptor ​dystroglycan via its alternative 3′-UTR. miR-310s gene expression fluctuates depending on ​dystroglycan amounts and ​nitric oxide signalling, which perceives ​dystroglycan levels and regulates microRNA gene expression. Aberrant levels of ​dystroglycan or deficiencies in miR-310s and ​nitric oxide signalling result in cobblestone brain appearance, resembling human lissencephaly type II phenotype

miRNA-based buffering of the cobblestone–lissencephaly-associated extracellular matrix receptor dystroglycan via its alternative 3′-UTR