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Human Molecular Genetics, 2001, Vol. 10, No. 17 1859-1866
© 2001 Oxford University Press

Identification of an endogenous RNA transcribed from the antisense strand of the HFE gene

Agnès C. Thénié, Isabelle M. Gicquel, Serge Hardy, Hélène Ferran, Patricia Fergelot, Jean-Yves Le Gall and Jean Mosser+

UMR-CNRS 6061, ‘Génétique et Développement’, 2 avenue du Pr Léon Bernard, CS 34317, 35043 Rennes cedex, France

Hereditary haemochromatosis is an autosomal recessive disease which results in iron overload, and it is the most frequently inherited disorder in Caucasian populations. The gene involved (HFE) has recently been identified, and it encodes an MHC class I-like molecule. A 2.7 kb cDNA has been isolated, whereas the HFE gene expression is characterized by an almost ubiquitous mRNA of 4.1 kb in size. The difference between this transcript and the isolated cDNA has not yet been explained. Thus, the 5' end of the HFE gene is still undefined and very little is known about the regulation of its expression. By searching this end, we isolated an antisense transcript originating from the same gene locus. Further investigations (rapid amplification of cDNA ends, RT–PCR experiments and dbEST screening) indicated that this RNA spans exon 1, exon 2, part of intron 1 of the HFE gene and ~1 kb upstream of it. This HFE antisense transcript is polyadenylated but displays no open reading frame. A ribonuclease A protection assay definitively demonstrated the biological existence of the HFE antisense RNA, which appears to be expressed in all of the tissues and cell lines tested. Furthermore, in vitro coupled transcription–translation experiments revealed that the HFE expression is decreased by this antisense RNA, indicating that it may play a critical role in the regulation of the HFE gene expression.

+ To whom correspondence should be addressed. Tel: +33 2 99 33 62 21; Fax: +33 2 99 33 62 00; Email: jean.mosser@univ-rennes1.fr Present address: Agnès C. Thénié, LEDAC,UMR 5538, Institut Albert Bonniot, Rond point de la Chantourne, 38706 La Tronche cedex, France


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