Heterogeneous nuclear ribonucleoprotein A1 is a novel internal ribosome entry site trans-acting factor that modulates alternative initiation of translation of the fibroblast growth factor 2 mRNA.

Sophie Bonnal (1) , Frédéric Pileur (1) , Cécile Orsini (2) , Fabienne Parker (2) , Françoise Pujol (1) , Anne-Catherine Prats (1) , Stéphan Vagner (1)

1 Hormones, facteurs de croissance et physiopathologie vasculaire
2 Sanofi-Aventis, Genomic sciences

Alternative initiation of translation of the human fibroblast growth factor 2 (FGF-2) mRNA at five in-frame CUG or AUG translation initiation codons requires various RNA cis-acting elements, including an internal ribosome entry site (IRES). Here we describe the purification of a trans-acting factor controlling FGF-2 mRNA translation achieved by several biochemical purification approaches. We have identified the heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as a factor that binds to the FGF-2 5'-leader RNA and that also complements defective FGF-2 translation in vitro in rabbit reticulocyte lysate. Recombinant hnRNP A1 stimulates in vitro translation at the four IRES-dependent initiation codons but has no effect on the cap-dependent initiation codon. Consistent with a role of hnRNP A1 in the control of alternative initiation of translation, short interfering RNA-mediated knock down of hnRNP A1 specifically inhibits translation at the four IRES-dependent initiation codons. Furthermore, hnRNP A1 binds to the FGF-2 IRES, implicating this interaction in the control of alternative initiation of translation.

Domaines: Médecine humaine et pathologie

Sophie Bonnal, Frédéric Pileur, Cécile Orsini, Fabienne Parker, Françoise Pujol, et al.. Heterogeneous nuclear ribonucleoprotein A1 is a novel internal ribosome entry site trans-acting factor that modulates alternative initiation of translation of the fibroblast growth factor 2 mRNA.. Journal of Biological Chemistry, 2005, 280 (6), pp.4144-53. ⟨10.1074/jbc.M411492200⟩. ⟨hal-00307810⟩