A novel H19 antisense RNA overexpressed in breast cancer contributes to paternal IGF2 expression.
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.
Berteaux
Nathalie
N
INSERM U908, Université des Sciences et Technologies de Lille, Bâtiment SN3, 59655 Villeneuve d'Ascq Cedex, France.
Aptel
Nathalie
N
Cathala
Guy
G
Genton
Céline
C
Coll
Jean
J
Daccache
Anthony
A
Spruyt
Nathalie
N
Hondermarck
Hubert
H
Dugimont
Thierry
T
Curgy
Jean-Jacques
JJ
Forné
Thierry
T
Adriaenssens
Eric
E
D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D021901:DNA, Intergenic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D021901:DNA, Intergenic; C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; C513121:IGF2 protein, mouse; D016372:RNA, Antisense; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II
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