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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

2004; Elsevier BV; Volume: 280; Issue: 6 Linguagem: Inglês

10.1074/jbc.m411492200

1083-351X

Sophie Bonnal, Frédéric Pileur, Cécile Orsini, Fabienne Parker, Françoise Pujol, Anne‐Catherine Prats, Stéphan Vagner,

RNA and protein synthesis mechanisms

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.