RESUMO
In the early Drosophila embryo, asymmetric distribution of transcription factors, established as a consequence of translational control of their maternally derived mRNAs, initiates pattern formation . For instance, translation of the uniformly distributed maternal hunchback (hb) mRNA is inhibited at the posterior to form an anterior-to-posterior protein concentration gradient along the longitudinal axis . Inhibition of hb mRNA translation requires an mRNP complex (the NRE complex), which consists of Nanos (Nos), Pumilio (Pum), and Brain tumor (Brat) proteins, and the Nos responsive element (NRE) present in the 3' UTR of hb mRNA . The identity of the mRNA 5' effector protein that is responsible for this translational inhibition remained elusive. Here we show that d4EHP, a cap binding protein that represses caudal (cad) mRNA translation , also inhibits hb mRNA translation by interacting simultaneously with the mRNA 5' cap structure (m(7)GpppN, where N is any nucleotide) and Brat. Thus, by regulating Cad and Hb expression, d4EHP plays a key role in establishing anterior-posterior axis polarity in the Drosophila embryo.
Assuntos
Padronização Corporal/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila/embriologia , Fator de Iniciação 4E em Eucariotos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , RNA Mensageiro Estocado/metabolismo , Animais , Western Blotting , Clonagem Molecular , Proteínas de Ligação a DNA/imunologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/imunologia , Embrião não Mamífero/fisiologia , Fator de Iniciação 4E em Eucariotos/genética , Imunofluorescência , Proteínas de Homeodomínio/metabolismo , Plasmídeos/genética , Fatores de Transcrição/metabolismoRESUMO
Translational control is a key genetic regulatory mechanism implicated in regulation of cell and organismal growth and early embryonic development. Initiation at the mRNA 5' cap structure recognition step is frequently targeted by translational control mechanisms. In the Drosophila embryo, cap-dependent translation of the uniformly distributed caudal (cad) mRNA is inhibited in the anterior by Bicoid (Bcd) to create an asymmetric distribution of Cad protein. Here, we show that d4EHP, an eIF4E-related cap binding protein, specifically interacts with Bcd to suppress cad translation. Translational inhibition depends on the Bcd binding region (BBR) present in the cad 3' untranslated region. Thus, simultaneous interactions of d4EHP with the cap structure and of Bcd with BBR renders cad mRNA translationally inactive. This example of cap-dependent translational control that is not mediated by canonical eIF4E defines a new paradigm for translational inhibition involving tethering of the mRNA 5' and 3' ends.