title: Fibroblast growth factor 1 induced during myogenesis by a transcription-translation coupling mechanism.
abstract: 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.
authors: Inserm, U858 and Institut de Médecine Moléculaire de Rangueil, Université de Toulouse, UPS, IFR150, F-31432 Toulouse, France.
authors: Caroline
authors: C
authors: Conte
authors: Nadera
authors: N
authors: Ainaoui
authors: Aurélie
authors: A
authors: Delluc-Clavières
authors: Marie P
authors: MP
authors: Khoury
authors: Rania
authors: R
authors: Azar
authors: Françoise
authors: F
authors: Pujol
authors: Yvan
authors: Y
authors: Martineau
authors: Stéphane
authors: S
authors: Pyronnet
authors: Anne-Catherine
authors: AC
authors: Prats
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D012038:Regeneration; D015533:Transcriptional Activation
chemical_list: D016220:Fibroblast Growth Factor 1