The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation

Understanding the molecular mechanisms that regulate cellular proliferation and differentiation is a central theme of developmental biology. MicroRNAs (miRNAs) are a class of regulatory RNAs of ∼22 nucleotides that post-transcriptionally regulate gene expression. Increasing evidence points to the potential role of miRNAs in various biological processes. Here we show that miRNA-1 (miR-1) and miRNA-133 (miR-133), which are clustered on the same chromosomal loci, are transcribed together in a tissue-specific manner during development. miR-1 and miR-133 have distinct roles in modulating skeletal muscle proliferation and differentiation in cultured myoblasts in vitro and in Xenopus laevis embryos in vivo. miR-1 promotes myogenesis by targeting histone deacetylase 4 (HDAC4), a transcriptional repressor of muscle gene expression. By contrast, miR-133 enhances myoblast proliferation by repressing serum response factor (SRF). Our results show that two mature miRNAs, derived from the same miRNA polycistron and transcribed together, can carry out distinct biological functions. Together, our studies suggest a molecular mechanism in which miRNAs participate in transcriptional circuits that control skeletal muscle gene expression and embryonic development.

[1]  H. Blau,et al.  Plasticity of the differentiated state. , 1985, Science.

[2]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[3]  G. Ruvkun,et al.  Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans , 1993, Cell.

[4]  J. Smith,et al.  Inhibition of Xbra transcription activation causes defects in mesodermal patterning and reveals autoregulation of Xbra in dorsal mesoderm. , 1996, Development.

[5]  K. Kroll,et al.  Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation. , 1996, Development.

[6]  A. Kahn,et al.  Growth and differentiation of C2 myogenic cells are dependent on serum response factor , 1996, Molecular and cellular biology.

[7]  E. Olson,et al.  Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases. , 2000, Molecular cell.

[8]  E. Olson,et al.  Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation , 2000, Nature.

[9]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[10]  Da-Zhi Wang,et al.  Activation of Cardiac Gene Expression by Myocardin, a Transcriptional Cofactor for Serum Response Factor , 2001, Cell.

[11]  R. Passier,et al.  Regulation of cardiac growth and development by SRF and its cofactors. , 2002, Cold Spring Harbor symposia on quantitative biology.

[12]  T. Tuschl,et al.  Identification of Tissue-Specific MicroRNAs from Mouse , 2002, Current Biology.

[13]  V. Ambros,et al.  Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation , 2004, Genome Biology.

[14]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[15]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[16]  Thomas Tuschl,et al.  Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing. , 2004, RNA.

[17]  C. Perou,et al.  A custom microarray platform for analysis of microRNA gene expression , 2004, Nature Methods.

[18]  A. Hatzigeorgiou,et al.  A combined computational-experimental approach predicts human microRNA targets. , 2004, Genes & development.

[19]  Phillip D Zamore,et al.  Sequence-Specific Inhibition of Small RNA Function , 2004, PLoS biology.

[20]  D. Bartel,et al.  MicroRNAs Modulate Hematopoietic Lineage Differentiation , 2004, Science.

[21]  Michael Zuker,et al.  MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression , 2004, Nature Genetics.

[22]  V. Ambros.  The functions of animal microRNAs , 2004, Nature.

[23]  Yong Zhao,et al.  Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis , 2005, Nature.

[24]  K. Gunsalus,et al.  Combinatorial microRNA target predictions , 2005, Nature Genetics.

[25]  F. Conlon,et al.  Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis , 2005, Development.

[26]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[27]  H. Horvitz,et al.  MicroRNA Expression in Zebrafish Embryonic Development , 2005, Science.

[28]  A. Nordheim,et al.  Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Anton J. Enright,et al.  Materials and Methods Figs. S1 to S4 Tables S1 to S5 References and Notes Micrornas Regulate Brain Morphogenesis in Zebrafish , 2022 .

[30]  Da-Zhi Wang,et al.  Modulation of Smooth Muscle Gene Expression by Association of Histone Acetyltransferases and Deacetylases with Myocardin , 2005, Molecular and Cellular Biology.