title: miR-155 inhibits expression of the MEF2A protein to repress skeletal muscle differentiation.
abstract: microRNAs (miRNAs) are 21-23-nucleotide non-coding RNAs. It has become more and more evident that this class of small RNAs plays critical roles in the regulation of gene expression at the post-transcriptional level. MEF2A is a member of the MEF2 (myogenic enhancer factor 2) family of transcription factors. Prior report showed that the 3'-untranslated region (3'-UTR) of the Mef2A gene mediated its repression; however, the molecular mechanism underlying this intriguing observation was unknown. Here, we report that MEF2A is repressed by miRNAs. We identify miR-155 as one of the primary miRNAs that significantly represses the expression of MEF2A. We show that knockdown of the Mef2A gene by siRNA impairs myoblast differentiation. Similarly, overexpression of miR-155 leads to the repression of endogenous MEF2A expression and the inhibition of myoblast differentiation. Most importantly, reintroduction of MEF2A in miR-155 overexpressed myoblasts was able to partially rescue the miR-155-induced myoblast differentiation defect. Our data therefore establish miR-155 as an important regulator of MEF2A expression and uncover its function in muscle gene expression and myogenic differentiation.
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Seok
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Mariko
authors.initials: M
authors.lastname: Tatsuguchi
authors.affiliation: Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Callis
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Aibin
authors.initials: A
authors.lastname: He
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: William T
authors.initials: WT
authors.lastname: Pu
authors.affiliation: Department of Cardiology, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115; Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, North Carolina 27599. Electronic address: dwang@enders.tch.harvard.edu.
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000502:physiology; D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation / Q000502:physiology*; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D064326:MEF2 Transcription Factors; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D018006:Myogenic Regulatory Factors