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Originally published In Press as doi:10.1074/jbc.M001156200 on June 29, 2000

J. Biol. Chem., Vol. 275, Issue 38, 29562-29569, September 22, 2000
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H19 RNA Binds Four Molecules of Insulin-like Growth Factor II mRNA-binding Protein*

Steffen RungeDagger , Finn Cilius Nielsen§, Jacob NielsenDagger , Jens Lykke-AndersenDagger , Ulla M. Wewer||, and Jan ChristiansenDagger **

From the Dagger  RNA Regulation Centre, Institute of Molecular Biology, and the || Institute of Molecular Pathology, University of Copenhagen, DK-1307 Copenhagen, the § Department of Clinical Biochemistry, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark

H19 RNA is a major oncofetal 2.5-kilobase untranslated RNA of unknown function. The maternally expressed H19 gene is located 90 kilobase pairs downstream from the paternally expressed insulin-like growth factor II (IGF-II) gene on human chromosome 11 and mouse chromosome 7; and due to their reciprocal imprinting and identical spatiotemporal expression, it is assumed that the two genes are functionally coupled. Here we show that human H19 RNA contains four attachment sites for the oncofetal IGF-II mRNA-binding protein (IMP) with apparent Kd values in the 0.4-1.3 nM range. The multiple attachment sites are clustered within a 700-nucleotide segment encoded by exons 4 and 5. This 3'-terminal segment targets H19 RNA to lamellipodia and perinuclear regions in dispersed fibroblasts where IMP is also localized. The results suggest that IMP participates in H19 RNA localization and provides a link between the IGF-II and H19 genes at post-transcriptional events during mammalian development.

* The work was supported by the Danish Cancer Society, the Novo Nordisk Foundation, and the Danish Natural Science and Medical Research Councils and their Biotek II Program.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Boyer Center for Molecular Medicine, Yale University, New Haven, CT 06536.

** To whom correspondence should be addressed: Dept. of Biological Chemistry, Inst. of Molecular Biology, University of Copenhagen, Sølvgade 83 H, DK-1307 Copenhagen K, Denmark. Tel.: 45-3532-2008; Fax: 45-3532-2040; E-mail: janchr@mermaid.molbio.ku.dk.

Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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