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Molecular and Cellular Biology, November 2008, p. 6731-6745, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.02103-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Novel H19 Antisense RNA Overexpressed in Breast Cancer Contributes to Paternal IGF2 Expression{triangledown} ,{dagger}

Nathalie Berteaux,1,3 Nathalie Aptel,2 Guy Cathala,2 Céline Genton,2 Jean Coll,3 Anthony Daccache,3 Nathalie Spruyt,3 Hubert Hondermarck,1 Thierry Dugimont,1 Jean-Jacques Curgy,1 Thierry Forné,2 and Eric Adriaenssens1*

INSERM U908, IFR 147 and Université Lille1, 59655 Villeneuve d'Ascq, France,1 Institut de Génétique Moléculaire, CNRS UMR 5535, Université Montpellier II, IFR 122, Montpellier, France,2 CNRS UMR 8161, IBL, Universités de Lille I et Lille II, Institut Pasteur, Lille, France3

Received 26 November 2007/ Returned for modification 14 January 2008/ Accepted 29 July 2008

The H19/IGFf2 locus belongs to a large imprinted domain located on human chromosome 11p15.5 (homologue to mouse distal chromosome 7). The H19 gene is expressed from the maternal allele, while IGF2 is paternally expressed. Natural antisense transcripts and intergenic transcription have been involved in many aspects of eukaryotic gene expression, including genomic imprinting and RNA interference. However, apart from the identification of some IGF2 antisense transcripts, few data are available on that topic at the H19/IGF2 locus. We identify here a novel transcriptional activity at both the human and the mouse H19/IGF2 imprinted loci. This activity occurs antisense to the H19 gene and has the potential to produce a single 120-kb transcript that we called the 91H RNA. This nuclear and short-lived RNA is not imprinted in mouse but is expressed predominantly from the maternal allele in both mice and humans within the H19 gene region. Moreover, the transcript is stabilized in breast cancer cells and overexpressed in human breast tumors. Finally, knockdown experiments showed that, in humans, 91H, rather than affecting H19 expression, regulates IGF2 expression in trans.

* Corresponding author. Mailing address: INSERM U908, Université des Sciences et Technologies de Lille, Bâtiment SN3, 59655 Villeneuve d'Ascq Cedex, France. Phone: 33 320 43 40 14. Fax: 33 320 43 40 38. E-mail: eric.adriaenssens{at}univ-lille1.fr

{triangledown} Published ahead of print on 15 September 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, November 2008, p. 6731-6745, Vol. 28, No. 22
0270-7306/08/$08.00+0     doi:10.1128/MCB.02103-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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