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Molecular and Cellular Biology, July 2003, p. 4991-5004, Vol. 23, No. 14
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.14.4991-5004.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of HuR in Skeletal Myogenesis through Coordinate Regulation of Muscle Differentiation Genes

Angélica Figueroa,1 Ana Cuadrado,1 Jinshui Fan,2 Ulus Atasoy,3 George E. Muscat,4 Pura Muñoz-Canoves,5 Myriam Gorospe,2* and Alberto Muñoz1

Instituto de Investigaciones Biomédicas ‘Alberto Sols,’ Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, 28029 Madrid,1 Centro de Regulación Genómica, 08003 Barcelona, Spain,5 Laboratory of Cellular and Molecular Biology, NIA-IRP, National Institutes of Health, Baltimore, Maryland 21224,2 Duke University School of Medicine, Durham, North Carolina 27710,3 Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia4

Received 26 March 2003/ Returned for modification 23 April 2003/ Accepted 1 May 2003

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.

* Corresponding author. Mailing address: Box 12, LCMB, NIA-IRP, NIH, 5600 Nathan Shock Dr., Baltimore, MD 21224. Phone: (410) 558-8443. Fax: (410) 558-8386. E-mail: myriam-gorospe{at}nih.gov.

Molecular and Cellular Biology, July 2003, p. 4991-5004, Vol. 23, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.14.4991-5004.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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