miR-30 Family microRNAs Regulate Myogenic Differentiation and Provide Negative Feedback on the microRNA Pathway

microRNAs (miRNAs) are short non-coding RNAs that can mediate changes in gene expression and are required for the formation of skeletal muscle (myogenesis). With the goal of identifying novel miRNA biomarkers of muscle disease, we profiled miRNA expression using miRNA-seq in the gastrocnemius muscles of dystrophic mdx4cv mice. After identifying a down-regulation of the miR-30 family (miR-30a-5p, -30b, -30c, -30d and -30e) when compared to C57Bl/6 (WT) mice, we found that overexpression of miR-30 family miRNAs promotes differentiation, while inhibition restricts differentiation of myoblasts in vitro. Additionally, miR-30 family miRNAs are coordinately down-regulated during in vivo models of muscle injury (barium chloride injection) and muscle disuse atrophy (hindlimb suspension). Using bioinformatics tools and in vitro studies, we identified and validated Smarcd2, Snai2 and Tnrc6a as miR-30 family targets. Interestingly, we show that by targeting Tnrc6a, miR-30 family miRNAs negatively regulate the miRNA pathway and modulate both the activity of muscle-specific miR-206 and the levels of protein synthesis. These findings indicate that the miR-30 family may be an interesting biomarker of perturbed muscle homeostasis and muscle disease.

[1]  H. Blau,et al.  Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy , 1988, Cell.

[2]  R. Weller,et al.  Role of the basement membrane in the regeneration of skeletal muscle , 1990, Neuropathology and applied neurobiology.

[3]  A. Emery.  Population frequencies of inherited neuromuscular diseases—A world survey , 1991, Neuromuscular Disorders.

[4]  S. Tenenbaum,et al.  A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique population of human mRNAs within novel cytoplasmic speckles. , 2002, Molecular biology of the cell.

[5]  K. Davies,et al.  Pharmacological strategies for muscular dystrophy , 2003, Nature Reviews Drug Discovery.

[6]  F. Guadagni,et al.  Requirement for down-regulation of the CCAAT-binding activity of the NF-Y transcription factor during skeletal muscle differentiation. , 2003, Molecular biology of the cell.

[7]  S. Bhattacharya,et al.  Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy , 2004, Acta Neuropathologica.

[8]  J. Yates,et al.  A role for the P-body component GW182 in microRNA function , 2005, Nature Cell Biology.

[9]  E. Chan,et al.  Disruption of GW bodies impairs mammalian RNA interference , 2005, Nature Cell Biology.

[10]  Daniel J. Blankenberg,et al.  Galaxy: a platform for interactive large-scale genome analysis. , 2005, Genome research.

[11]  A. Malhotra,et al.  Muscle-specific microRNA miR-206 promotes muscle differentiation , 2006, The Journal of cell biology.

[12]  Jian-Fu Chen,et al.  The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation , 2006, Nature Genetics.

[13]  M. Hentze,et al.  A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domain , 2007, Nature Structural &Molecular Biology.

[14]  B. Spiegelman,et al.  PGC-1alpha regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy. , 2007, Genes & development.

[15]  B. Spiegelman,et al.  PGC-1α regulates the neuromuscular junction program and ameliorates Duchenne muscular dystrophy , 2007 .

[16]  Michael T. McManus,et al.  Essential role for Dicer during skeletal muscle development. , 2007, Developmental biology.

[17]  E. Izaurralde,et al.  P bodies: at the crossroads of post-transcriptional pathways , 2007, Nature Reviews Molecular Cell Biology.

[18]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[19]  N. Rajewsky,et al.  Widespread changes in protein synthesis induced by microRNAs , 2008, Nature.

[20]  D. Bartel,et al.  The impact of microRNAs on protein output , 2008, Nature.

[21]  Cole Trapnell,et al.  Ultrafast and memory-efficient alignment of short DNA sequences to the human genome , 2009, Genome Biology.

[22]  L. Kunkel,et al.  Correction for Eisenberg et al., Distinctive patterns of microRNA expression in primary muscular disorders , 2008, Proceedings of the National Academy of Sciences.

[23]  E. Olson,et al.  A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. , 2009, Developmental cell.

[24]  J. Friedman,et al.  The microRNA-30 family is required for vertebrate hepatobiliary development. , 2009, Gastroenterology.

[25]  R. Duisters,et al.  MIRNA-133 AND MIRNA-30 REGULATE CONNECTIVE TISSUE GROWTH FACTOR: IMPLICATIONS FOR A ROLE OF MIRNAS IN MYOCARDIAL MATRIX REMODELING , 2013 .

[26]  U. Tran,et al.  The miR-30 miRNA family regulates Xenopus pronephros development and targets the transcription factor Xlim1/Lhx1 , 2009, Development.

[27]  G. Meola,et al.  Common micro‐RNA signature in skeletal muscle damage and regeneration induced by Duchenne muscular dystrophy and acute ischemia , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  Paul Bertone,et al.  Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. , 2010, RNA.

[29]  Jincheng Li,et al.  miR-30 Regulates Mitochondrial Fission through Targeting p53 and the Dynamin-Related Protein-1 Pathway , 2010, PLoS genetics.

[30]  L. Fritsch,et al.  The Core Binding Factor CBF Negatively Regulates Skeletal Muscle Terminal Differentiation , 2010, PloS one.

[31]  K. Bushby,et al.  Molecular treatments in Duchenne muscular dystrophy. , 2010, Current opinion in pharmacology.

[32]  B. Harrison,et al.  IIb or not IIb? Regulation of myosin heavy chain gene expression in mice and men , 2011, Skeletal Muscle.

[33]  Patrick J. Biggs,et al.  SolexaQA: At-a-glance quality assessment of Illumina second-generation sequencing data , 2010, BMC Bioinformatics.

[34]  Anindya Dutta,et al.  miR-206 and -486 Induce Myoblast Differentiation by Downregulating Pax7 , 2010, Molecular and Cellular Biology.

[35]  Ana M. Aransay,et al.  miRanalyzer: an update on the detection and analysis of microRNAs in high-throughput sequencing experiments , 2011, Nucleic Acids Res..

[36]  C. Dani,et al.  Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis , 2011, Genome Biology.

[37]  J. Zavadil,et al.  miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis. , 2011, Cancer cell.

[38]  D. Bartel,et al.  Weak Seed-Pairing Stability and High Target-Site Abundance Decrease the Proficiency of lsy-6 and Other miRNAs , 2011, Nature Structural &Molecular Biology.

[39]  J. Lingner,et al.  AUF1/HnRNP D RNA binding protein functions in telomere maintenance. , 2012, Molecular cell.

[40]  T. Thum,et al.  A phenotypic screen to identify hypertrophy-modulating microRNAs in primary cardiomyocytes. , 2012, Journal of molecular and cellular cardiology.

[41]  M. Rudnicki,et al.  Snail regulates MyoD binding-site occupancy to direct enhancer switching and differentiation-specific transcription in myogenesis. , 2012, Molecular cell.

[42]  R. Green,et al.  miRNA-Mediated Gene Silencing by Translational Repression Followed by mRNA Deadenylation and Decay , 2012, Science.

[43]  T. Dalmay,et al.  Regulation of multiple target genes by miR-1 and miR-206 is pivotal for C2C12 myoblast differentiation , 2012, Journal of Cell Science.

[44]  Junfeng Zhang,et al.  miR-30 inhibits TGF-β1-induced epithelial-to-mesenchymal transition in hepatocyte by targeting Snail1. , 2012, Biochemical and biophysical research communications.

[45]  Tom H. Cheung,et al.  Maintenance of muscle stem cell quiescence by microRNA-489 , 2012, Nature.

[46]  P. Muñoz-Cánoves,et al.  PAI-1–regulated miR-21 defines a novel age-associated fibrogenic pathway in muscular dystrophy , 2012, The Journal of cell biology.

[47]  E. Olson,et al.  microRNA-206 promotes skeletal muscle regeneration and delays progression of Duchenne muscular dystrophy in mice. , 2012, The Journal of clinical investigation.

[48]  Haibo Zhou,et al.  miR-30 Family Members Negatively Regulate Osteoblast Differentiation* , 2012, The Journal of Biological Chemistry.

[49]  Daiwen Chen,et al.  MicroRNA-27a promotes myoblast proliferation by targeting myostatin. , 2012, Biochemical and biophysical research communications.

[50]  M. Gering,et al.  The miR-30 MicroRNA Family Targets smoothened to Regulate Hedgehog Signalling in Zebrafish Early Muscle Development , 2013, PloS one.

[51]  L. Leinwand,et al.  Measuring microRNA reporter activity in skeletal muscle using hydrodynamic limb vein injection of plasmid DNA combined with in vivo imaging , 2013, Skeletal Muscle.

[52]  K. Ui-Tei,et al.  Human TNRC6A is an Argonaute-navigator protein for microRNA-mediated gene silencing in the nucleus. , 2013, RNA.

[53]  L. Leinwand,et al.  Molecular consequences of the R453C hypertrophic cardiomyopathy mutation on human β-cardiac myosin motor function , 2013, Proceedings of the National Academy of Sciences.

[54]  P. Visca,et al.  Cyclin D1 is a major target of miR-206 in cell differentiation and transformation , 2013, Cell cycle.

[55]  Andrea M. Hanson,et al.  Longitudinal characterization of functional, morphologic, and biochemical adaptations in mouse skeletal muscle with hindlimb suspension , 2013, Muscle & nerve.

[56]  张静,et al.  Banana Ovate family protein MaOFP1 and MADS-box protein MuMADS1 antagonistically regulated banana fruit ripening , 2015 .