Muscle-specific microRNA miR-206 promotes muscle differentiation.
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 alpha 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.
Kim
Hak Kyun
HK
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
Lee
Yong Sun
YS
Sivaprasad
Umasundari
U
Malhotra
Ankit
A
Dutta
Anindya
A
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D004256:DNA Polymerase I / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection
D051792:Basic Helix-Loop-Helix Proteins; D018031:Connexin 43; D004256:DNA Polymerase I; D008222:Lymphokines; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C485841:Hspc121 protein, mouse; C117673:Msc protein, mouse; C050979:monocyte-macrophage differentiation factor