title: Zebrafish miR-1 and miR-133 shape muscle gene expression and regulate sarcomeric actin organization.
abstract: microRNAs (miRNAs) represent approximately 4% of the genes in vertebrates, where they regulate deadenylation, translation, and decay of the target messenger RNAs (mRNAs). The integrated role of miRNAs to regulate gene expression and cell function remains largely unknown. Therefore, to identify the targets coordinately regulated by muscle miRNAs in vivo, we performed gene expression arrays on muscle cells sorted from wild type, dicer mutants, and single miRNA knockdown embryos. Our analysis reveals that two particular miRNAs, miR-1 and miR-133, influence gene expression patterns in the zebrafish embryo where they account for >54% of the miRNA-mediated regulation in the muscle. We also found that muscle miRNA targets (1) tend to be expressed at low levels in wild-type muscle but are more highly expressed in dicer mutant muscle, and (2) are enriched for actin-related and actin-binding proteins. Loss of dicer function or down-regulation of miR-1 and miR-133 alters muscle gene expression and disrupts actin organization during sarcomere assembly. These results suggest that miR-1 and miR-133 actively shape gene expression patterns in muscle tissue, where they regulate sarcomeric actin organization.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mishima
authors.forename: Cei
authors.initials: C
authors.lastname: Abreu-Goodger
authors.forename: Alison A
authors.initials: AA
authors.lastname: Staton
authors.forename: Carlos
authors.initials: C
authors.lastname: Stahlhut
authors.forename: Chong
authors.initials: C
authors.lastname: Shou
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Enright
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Giraldez
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D035683:MicroRNAs / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D012518:Sarcomeres / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D035683:MicroRNAs; D012333:RNA, Messenger; D029961:Zebrafish Proteins