miRNAs and musculature

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miRNAs and musculature

(Note: for more on microRNAs and gene therapy go to our Files section to

the Research File, click to open and read my recent piece on MicroRNAS, entitled

" Gorrillas in our Midst " .)

~ Gretchen

http://www.medicalnewstoday.com/medicalnews.php?newsid=30667

16 Sep 2005

In an effort to understand the biological function of the microRNA

mir1, Drs 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). Mir-1 is an

evolutionarily conserved miRNA, whose expression in mouse and humans

is limited to heart and skeletal muscle. 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.

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.