Abstract
In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3' Untranslated Regions
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Animals
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Antigens, Surface*
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Base Sequence
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Cell Differentiation / drug effects
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Cell Differentiation / genetics
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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Cytoplasm / drug effects
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Cytoplasm / genetics
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Cytoplasm / metabolism
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ELAV Proteins
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ELAV-Like Protein 1
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Gene Expression Regulation, Developmental*
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Half-Life
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Insulin / pharmacology
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Muscle Development / physiology*
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Muscle, Skeletal / cytology
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Muscle, Skeletal / physiology*
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MyoD Protein / genetics
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Myoblasts / physiology
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Myogenin / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / physiology*
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Regeneration / genetics
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Selenium / pharmacology
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Transferrin / pharmacology
Substances
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3' Untranslated Regions
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Antigens, Surface
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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ELAV Proteins
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ELAV-Like Protein 1
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ELAVL1 protein, human
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Insulin
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MyoD Protein
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Myog protein, mouse
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Myogenin
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RNA, Messenger
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RNA-Binding Proteins
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Transferrin
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Selenium