@article{9fb22f33ffac41ccac0a0168147157f2,
title = "Zebrafish miR-1 and miR-133 shape muscle gene expression and regulate sarcomeric actin organization",
abstract = "microRNAs (miRNAs) represent ∼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.",
keywords = "MicroRNAs, Muscle, Target identification, Zebrafish",
author = "Yuichiro Mishima and Cei Abreu-Goodger and Staton, {Alison A.} and Carlos Stahlhut and Chong Shou and Chao Cheng and Mark Gerstein and Enright, {Anton J.} and Giraldez, {Antonio J.}",
note = "We thank W. Huttner and D. De Pietri for the dual GFP-RFP reporter construct; K. Kawakami for the tol2 vector; and T. Pollard, S. Weatherbee, M. Hammarlund, M. Khokha, V. Greco, J. Noonan, R. Yi, H. Knaut, C. Takacs, D. Cifuentes, and B. Schachter for discussions and comments on the manuscript. We thank Robert Andrews for suggesting Stouffer{\textquoteright}s method for combining P-values. We thank the MSKCC for the microarray analysis and the FACS facility at Yale. We thank T.H. Kim for his advice during qRT–PCR analysis. Y.M. was supported by a JSPS post-doctoral fellowship for research abroad. A.J.G. is a Pew Fellow Lois and Franklin Top Yale Scholar. This project was funded by the Pew foundation, The Yale Scholar Program, and the Muscular Dystrophy Association. Individual contributions were as follows: Y.M. and A.J.G. designed the project; Y.M. performed the experiments, microarray analysis, and target analysis. Y.M. and A.J.G. wrote the paper. A.A.S. and C.S. generated the miR-1 reporter transgenic and analyzed their expression. A.J.E. and C.A.G. did the microarray analysis, sylamer plots, and initial target site enrichment, 39UTR data set, and Gene ontology analysis. C.S., C.C., and M.G. performed PPIN analysis and GO analysis. ",
year = "2009",
month = mar,
day = "1",
doi = "10.1101/gad.1760209",
language = "English",
volume = "23",
pages = "619--632",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "5",
}