Homeodomain position 54 specifies transcriptional versus translational control by bicoid

Bicoid (BCD), the anterior determinant of Drosophila, controls embryonic ge ne expression by transcriptional activation and translational repression. B oth functions require the homeodomain (HD), which recognizes DNA motifs at target gene enhancers and a specific sequence interval in the 3' untranslat ed region of caudal (cad) mRNA. Here we show that the BCD HD is a nucleic a cid-binding unit. Its helix III contains an arginine-rich motif (ARM), simi lar to the RNA-binding domain of the HIV-1 protein REV, needed for both RNA and DNA recognition. Replacement of arginine 54, within this motif, alters the RNA but not the DNA binding properties of the HD. Corresponding BCD mu tants fail to repress cad mRNA translation, whereas the transcriptional tar get genes are still activated.