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Volume 272, Number 9, Issue of February 28, 1997 pp. 5995-6003
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Characterization of Two Age-induced Intracisternal A-particle-related Transcripts in the Mouse Liver
TRANSCRIPTIONAL READ-THROUGH INTO AN OPEN READING FRAME WITH SIMILARITIES TO THE YEAST CCR4 TRANSCRIPTION FACTOR

(Received for publication, September 13, 1996, and in revised form, November 18, 1996)

Anne Puech Dagger , Anne Dupressoir Dagger , Marie-Paule Loireau Dagger , Marie-Geneviève Mattei par and Thierry Heidmann Dagger

From the Dagger  Unité de Physicochimie et Pharmacologie des Macromolécules Biologiques, CNRS URA147, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, and par  Unité de Génétique Médicale et Développement, INSERM U406, Faculté de Médecine, 27, Bd. Jean Moulin, 13385 Marseille, France

Intracisternal A-particle (IAP) sequences are endogenous retrovirus-like elements present at 1,000 copies in the mouse genome. We had previously identified IAP-related transcripts of unusual size (6 and 10 kilobases (kb)), which are observed exclusively in the liver of the aging mouse. In this report, using cDNA libraries that we have constructed from the liver mRNAs of an aged DBA/2 mouse, we have cloned and entirely sequenced the corresponding cDNAs. Both are initiated within the 5' long terminal repeat of a type IDelta 1 IAP sequence, and correspond to a read-through into a unique flanking cellular sequence containing a 966-nucleotide open reading frame, located 3' to the IAP sequence. The 6-kb IAP-related transcript corresponds to a post-transcriptional modification of the 10-kb mRNA, and is generated by a splicing event with the donor site in the IAP sequence, and the acceptor site 5' to the open reading frame. This open reading frame is located on chromosome 3, is evolutionarily conserved, and discloses significant similarity to the yeast CCR4 transcription factor at the amino acid level. The specific expression of these age-induced transcripts, which account for more than 50% of the IAP-related transcripts in the liver of old mice, is therefore entirely consistent with the induction of a single genomic locus, thus strengthening the importance of position effects for the expression of transposable elements. Characterization of this locus should now allow studies on its chromatin and methylation status, and on the "molecular factors of senescence" possibly involved in its induction.


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