Micro RNAs And Musculature
- Date:
- September 15, 2005
- Source:
- Cold Spring Harbor Laboratory
- Summary:
- In an effort to understand the biological function of the microRNA mir1, Drs. Nicholas Sokol and Victor Ambros (Darmouth Medical School) have studied the expression profile, transcriptional regulation and loss-of-function phenotype of Drosophila mir-1 (Dmir-1). Strikingly, their study shows that, in Drosophila embryos, mir-1 expression is not required for mesodermal cell fate decisions or cell proliferation during embryogenesis, but rather, that it appears to act to reinforce and maintain cell identity during times of rapid growth.
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In an effort to understand the biological function of the microRNAmir1, Drs. Nicholas Sokol and Victor Ambros (Darmouth Medical School)have studied the expression profile, transcriptional regulation andloss-of-function phenotype of Drosophila mir-1 (Dmir-1). Mir-1 is anevolutionarily conserved miRNA, whose expression in mouse and humans islimited to heart and skeletal muscle. Strikingly, their study showsthat, in Drosophila embryos, mir-1 expression is not required formesodermal cell fate decisions or cell proliferation duringembryogenesis, but rather, that it appears to act to reinforce andmaintain cell identity during times of rapid growth.
The authors find that, as in zebrafish, mouse and humans, Dmir-1 isspecifically expressed in muscle cells. Furthermore, they show thatDmir-1 expression is regulated by the promesodermal transcriptionfactor Twist and the promyogenic transcription factor Mef2, thusplacing Dmir-1 within established transcriptional networks in muscle.However, the authors find that muscles form normally in embryos inwhich expression of Dmir-1 has been ablated by gene targeting (Dmir-1KO). A defect is only revealed when larval growth is initiated byfeeding, which triggers paralysis and eventually death of Dmir-1 KOlarvae.
Analysis of the mutant larvae after feeding reveals disrupted somaticmusculature, strongly suggesting a role for Dmir-1 in the maintenanceof muscle integrity and identity in times of stress induced by growth.Dr. Sokol proposes that "Mir-1 could function generally to maintainmuscle cell identity by ensuring that mRNAs from promiscuouslytranscribed nonmuscle genes remain inactive." Their work adds to theemerging range of functions that miRNAs perform in an organism andadvocates the study of loss-of-function mutations in miRNA genes as anessential tool for identifying the biological roles of miRNAs.
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