Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes.
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.
Figueroa
Angélica
A
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Cuadrado
Ana
A
Fan
Jinshui
J
Atasoy
Ulus
U
Muscat
George E
GE
Muñoz-Canoves
Pura
P
Gorospe
Myriam
M
Muñoz
Alberto
A
D020413:3' Untranslated Regions; D000818:Animals; D000954:Antigens, Surface; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D003593:Cytoplasm / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D018507:Gene Expression Regulation, Developmental; D006207:Half-Life; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000502:physiology; D018008:Myogenin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D012038:Regeneration / Q000235:genetics; D012643:Selenium / Q000494:pharmacology; D014168:Transferrin / Q000494:pharmacology
D020413:3' Untranslated Regions; D000954:Antigens, Surface; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D007328:Insulin; D017570:MyoD Protein; C503801:Myog protein, mouse; D018008:Myogenin; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014168:Transferrin; D012643:Selenium