H19 RNA binds four molecules of insulin-like growth factor II mRNA-bindingprotein

H19 RNA is a major oncofetal 2.5-kilobase untranslated RNA of unknown funct ion. The maternally expressed H19 gene is located 90 kilobase pairs downstr eam from the paternally expressed insulin-like growth factor II (IGF-II) ge ne on human chromosome 11 and mouse chromosome 7; and due to their reciproc al imprinting and identical spatiotemporal expression, it is assumed that t he two genes are functionally coupled. Here we show that human H19 RNA cont ains four attachment sites for the oncofetal IGF-II mRNA-binding protein (I MP) with apparent K-d values in the 0.4-1.3 nM range. The multiple attachme nt sites are clustered within a 700-nucleotide segment encoded by exons 4 a nd 5. This 3'-terminal segment targets H19 RNA to lamellipodia and perinucl ear regions in dispersed fibroblasts where IMP is also localized. The resul ts suggest that IMP participates in H19 RNA localization and provides a lin k between the IGF-II and H19 genes at post-transcriptional events during ma mmalian development.