The authors find that, as in zebrafish, mouse and humans, Dmir-1 is specifically expressed in muscle cells. Furthermore, they show that Dmir-1 expression is regulated by the promesodermal transcription factor Twist and the promyogenic transcription factor Mef2, thus placing Dmir-1 within established transcriptional networks in muscle. However, the authors find that muscles form normally in embryos in which expression of Dmir-1 has been ablated by gene targeting (Dmir-1 KO). A defect is only revealed when larval growth is initiated by feeding, which triggers paralysis and eventually death of Dmir-1 KO larvae.
Analysis of the mutant larvae after feeding reveals disrupted somatic musculature, strongly suggesting a role for Dmir-1 in the maintenance of muscle integrity and identity in times of stress induced by growth. Dr. Sokol proposes that "Mir-1 could function generally to maintain muscle cell identity by ensuring that mRNAs from promiscuously transcribed nonmuscle genes remain inactive." Their work adds to the emerging range of functions that miRNAs perform in an organism and advocates the study of loss-of-function mutations in miRNA genes as an essential tool for identifying the biological roles of miRNAs.
Genes & Development