Nucleic Acids Research Advance Access originally published online on June 26, 2009
Nucleic Acids Research 2009 37(16):5267-5278; doi:10.1093/nar/gkp550
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Nucleic Acids Research, 2009, Vol. 37, No. 16 5267-5278
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gene Regulation, Chromatin and Epigenetics |
Fibroblast growth factor 1 induced during myogenesis by a transcription–translation coupling mechanism
Inserm, U858 and Institut de Médecine Moléculaire de Rangueil, Université de Toulouse, UPS, IFR150, F-31432 Toulouse, France
*To whom correspondence should be addressed. Tel: +33 5613 22143; Fax: +33 5613 25622; Email: anne-catherine.prats{at}inserm.fr
Received January 23, 2009. Revised June 9, 2009. Accepted June 11, 2009.
Fibroblast growth factor 1 (FGF1) is involved in muscle development and regeneration. The FGF1 gene contains four tissue-specific promoters allowing synthesis of four transcripts with distinct leader regions. Two of these transcripts contain internal ribosome entry sites (IRESs), which are RNA elements allowing mRNA translation to occur in conditions of blockade of the classical cap-dependent mechanism. Here, we investigated the function and the regulation of FGF1 during muscle differentiation and regeneration. Our data show that FGF1 protein expression is induced in differentiating myoblasts and regenerating mouse muscle, whereas siRNA knock-down demonstrated FGF1 requirement for myoblast differentiation. FGF1 induction occurred at both transcriptional and translational levels, involving specific activation of both promoter A and IRES A, whereas global cap-dependent translation was inhibited. Furthermore, we identified, in the FGF1 promoter A distal region, a cis-acting element able to activate the IRES A-driven translation. These data revealed a mechanism of molecular coupling of mRNA transcription and translation, involving a unique process of IRES activation by a promoter element. The crucial role of FGF1 in myoblast differentiation provides physiological relevance to this novel mechanism. This finding also provides a new insight into the molecular mechanisms linking different levels of gene expression regulation.