Potent activation of FGF-2 IRES-dependent mechanism of translation during brain development.

Sylvie Audigier (1) , Janique Guiramand (2) , Leonel Prado-Lourenco (3) , Caroline Conte (4) , Irma Gabriela Gonzalez-Herrera (3) , Catherine Cohen-Solal (2) , Max Récasens , Anne-Catherine Prats (3)

1 IFR 31 - IFR 31 Louis Bugnard
2 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
3 Hormones, facteurs de croissance et physiopathologie vasculaire
4 I2MR - Institut de médecine moléculaire de Rangueil

Fibroblast growth factor-2 (FGF-2) plays a fundamental role in brain functions. This role may be partly achieved through the control of its expression at the translational level via an internal ribosome entry site (IRES)-dependent mechanism. Transgenic mice expressing a bicistronic mRNA allowed us to study in vivo and ex vivo where this translational mechanism operates. Along brain development, we identified a stringent spatiotemporal regulation of FGF-2 IRES activity showing a peak at post-natal day 7 in most brain regions, which is concomitant with neuronal maturation. At adult age, this activity remained relatively high in forebrain regions. By the enrichment of this activity in forebrain synaptoneurosomes and by the use of primary cultures of cortical neurons or cocultures with astrocytes, we showed that this activity is indeed localized in neurons, is dependent on their maturation, and correlates with endogenous FGF-2 protein expression. In addition, this activity was regulated by astrocyte factors, including FGF-2, and spontaneous electrical activity. Thus, neuronal IRES-driven translation of the FGF-2 mRNA may be involved in synapse formation and maturation.

Mots clés: FGF-2; protein synthesis; IRES; development; brain; neuron

Domaines: Neurosciences [q-bio.NC]

Sylvie Audigier, Janique Guiramand, Leonel Prado-Lourenco, Caroline Conte, Irma Gabriela Gonzalez-Herrera, et al.. Potent activation of FGF-2 IRES-dependent mechanism of translation during brain development.. RNA, 2008, 14 (9), pp.1852-64. ⟨10.1261/rna.790608⟩. ⟨hal-00397548⟩