A family of IGF-II mRNA binding proteins (IMP) involved in RNA trafficking

Abstract

During a search for trans-acting factors associating with insulin-like growth factor II (IGF-II) mRNAs, we recently identified a family of three IGF-II mRNA-binding Proteins (IMP1, IMP2 and IMP3) that exhibit multiple attachments to IGF-II leader 3 mRNA and the reciprocally imprinted H19 RNA. IMPs contain the unique combination of two RNA recognition motifs (RRMs) and four hnRNP K homology (KH) domains. IMP1 is orthologous to the chicken zipcode-binding protein (ZBP-1), and the mouse c-myc coding region determinant-binding protein (CRD-BP) that associates with beta-actin and c-myc mRNA, respectively. Moreover, the p62 protein identified in hepatocellular carcinoma represents a splice variant of IMP2, and IMP3 is orthologous to the Xenopus Vegetal 1 RNA-binding protein (Vgl-RBP/Vera). IMPs are produced in a biphasic fashion--initially during the early stages of embryogenesis and subsequently later in development. IMPs and their orthologues are predominantly cytoplasmic and are implicated in the transport of their RNA targets towards the leading edge in somatic cells and to the vegetal pole in Xenopus oocytes, respectively. RNA localization is a conserved mechanism of polarizing genetic information in the establishment of asymmetries during both embryogenesis and adult life, enabling local protein synthesis at final destinations within the cell. The identification of developmentally expressed zipcode-binding proteins indicates that RNA trafficking participates in processes such as cell-growth and migration during embryogenesis.