Vg1 mRNA translocation to the vegetal cortex of Xenopus oocytes requires intact microtubules, and a 3' UTR cia-acting element (termed VLE), which also mediates sequence-specific binding of several proteins. One protein, the 69-kD Vg1 REP, associates Vg1 RNA to microtubules in vitro. Here we show that Vg1 REP-binding sites correlate with vegetal localization. Purification and cloning of Vg1 REP revealed five RNA-binding motifs: four KH and one RRM domains. Surprisingly, Vg1 REP is highly homologous to the zipcode binding protein implicated in the microfilament-mediated localization of beta actin mRNA in fibroblasts. These data support Vg1 RBP's direct role in vegetal localization and suggest the existence of a general, evolutionarily conserved mechanism for mRNA targeting.