Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
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 approximately 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.
Ambros,
The functions of animal microRNAs.
2004, Pubmed
Ambros,
The functions of animal microRNAs.
2004,
Pubmed Bartel,
MicroRNAs: genomics, biogenesis, mechanism, and function.
2004,
Pubmed Blau,
Plasticity of the differentiated state.
1985,
Pubmed Brown,
Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis.
2005,
Pubmed
,
Xenbase Cao,
Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin.
2005,
Pubmed Chen,
MicroRNAs modulate hematopoietic lineage differentiation.
2004,
Pubmed Conlon,
Inhibition of Xbra transcription activation causes defects in mesodermal patterning and reveals autoregulation of Xbra in dorsal mesoderm.
1996,
Pubmed
,
Xenbase Giraldez,
MicroRNAs regulate brain morphogenesis in zebrafish.
2005,
Pubmed He,
A microRNA polycistron as a potential human oncogene.
2005,
Pubmed Hutvágner,
Sequence-specific inhibition of small RNA function.
2004,
Pubmed Kiriakidou,
A combined computational-experimental approach predicts human microRNA targets.
2004,
Pubmed Krek,
Combinatorial microRNA target predictions.
2005,
Pubmed Kroll,
Transgenic Xenopus embryos from sperm nuclear transplantations reveal FGF signaling requirements during gastrulation.
1996,
Pubmed
,
Xenbase Lagos-Quintana,
Identification of tissue-specific microRNAs from mouse.
2002,
Pubmed Lee,
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
1993,
Pubmed Lee,
An extensive class of small RNAs in Caenorhabditis elegans.
2001,
Pubmed Lewis,
Prediction of mammalian microRNA targets.
2003,
Pubmed Li,
Requirement for serum response factor for skeletal muscle growth and maturation revealed by tissue-specific gene deletion in mice.
2005,
Pubmed Lu,
Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases.
2000,
Pubmed Mansfield,
MicroRNA-responsive 'sensor' transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression.
2004,
Pubmed McKinsey,
Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation.
2000,
Pubmed Meister,
Sequence-specific inhibition of microRNA- and siRNA-induced RNA silencing.
2004,
Pubmed Sempere,
Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation.
2004,
Pubmed Soulez,
Growth and differentiation of C2 myogenic cells are dependent on serum response factor.
1996,
Pubmed Thomson,
A custom microarray platform for analysis of microRNA gene expression.
2004,
Pubmed Wang,
Regulation of cardiac growth and development by SRF and its cofactors.
2002,
Pubmed
,
Xenbase Wang,
Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor.
2001,
Pubmed
,
Xenbase Wienholds,
MicroRNA expression in zebrafish embryonic development.
2005,
Pubmed Wightman,
Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.
1993,
Pubmed Zhao,
Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis.
2005,
Pubmed
