Muscle-specific microRNA miR-206 promotes muscle differentiation

Kyun Kim Hak, Sun Lee Yong, Umasundari Sivaprasad, Ankit Malhotra, Anindya Dutta

Research output: Contribution to journalArticle

549 Scopus citations

Abstract

Three muscle-specific microRNAs, miR-206, -1, and -133, are induced during differentiation of C2C12 myoblasts in vitro. Transfection of miR-206 promotes differentiation despite the presence of serum, whereas inhibition of the microRNA by antisense oligonucleotide inhibits cell cycle withdrawal and differentiation, which are normally induced by serum deprivation. Among the many mRNAs that are down-regulated by miR-206, the p180 subunit of DNA polymerase a and three other genes are shown to be direct targets. Down-regulation of the polymerase inhibits DNA synthesis, an important component of the differentiation program. The direct targets are decreased by mRNA cleavage that is dependent on predicted microRNA target sites. Unlike small interfering RNA-directed cleavage, however, the 5′ ends of the cleavage fragments are distributed and not confined to the target sites, suggesting involvement of exonucleases in the degradation process. In addition, inhibitors of myogenic transcription factors, Id1-3 and MyoR, are decreased upon miR-206 introduction, suggesting the presence of additional mechanisms by which microRNAs enforce the differentiation program.

Original languageEnglish (US)
Pages (from-to)677-687
Number of pages11
JournalJournal of Cell Biology
Volume174
Issue number5
DOIs
StatePublished - Aug 28 2006
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hak, K. K., Yong, S. L., Sivaprasad, U., Malhotra, A., & Dutta, A. (2006). Muscle-specific microRNA miR-206 promotes muscle differentiation. Journal of Cell Biology, 174(5), 677-687. https://doi.org/10.1083/jcb.200603008