MUNC, a Long Noncoding RNA That Facilitates the Function of MyoD in Skeletal Myogenesis Journal Article uri icon



  • Anin silicoscreen for myogenic long noncoding RNAs (lncRNAs) revealed nine lncRNAs that are upregulated more than 10-fold in myotubes versus levels in myoblasts. One of these lncRNAs, MyoD upstream noncoding (MUNC, also known as DRReRNA), is encoded 5 kb upstream of the transcription start site ofMyoD, a myogenic transcription factor gene. MUNC is specifically expressed in skeletal muscle and exists as in unspliced and spliced isoforms, and its 5′ end overlaps with thecis-acting distal regulatory region (DRR) ofMyoD. Small interfering RNA (siRNA) of MUNC reduced myoblast differentiation and specifically reduced the association of MyoD to the DRR enhancer and myogenin promoter but not to another MyoD-dependent enhancer. Stable overexpression of MUNC from a heterologous promoter increased endogenousMyoD,Myogenin, andMyh3(myosin heavy chain, [MHC] gene) mRNAs but not the cognate proteins, suggesting that MUNC can act intransto promote gene expression but that this activity does not require an induction of MyoD protein. MUNC also stimulates the transcription of other genes that are not recognized as MyoD-inducible genes. Knockdown of MUNCin vivoimpaired murine muscle regeneration, implicating MUNC in primary satellite cell differentiation in the animal. We also discovered a human MUNC that is induced during differentiation of myoblasts and whose knockdown decreases differentiation, suggesting an evolutionarily conserved role of MUNC lncRNA in myogenesis. Although MUNC overlaps with the DRR enhancer, our results suggest that MUNC is not a classiccis-acting enhancer RNA (e-RNA) acting exclusively by stimulating the neighboringMyoDgene but more like a promyogenic lncRNA that acts directly or indirectly on multiple promoters to increase myogenic gene expression.

publication date

  • February 1, 2015

Full Author List

  • Mueller AC; Cichewicz MA; Dey BK; Layer R; Reon BJ; Gagan JR; Dutta A

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Additional Document Info

start page

  • 498

end page

  • 513


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