CHARACTERIZATION OF 2 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

Intracisternal A-particle (IAP) sequences are endogenous retrovirus-li ke elements present at 1,000 copies in the mouse genome, We had previo usly identified IAP-related transcripts of unusual size (6 and 10 kilo bases (kb)), which are observed exclusively in the liver of the aging mouse. In this report, using cDNA libraries that we have constructed f rom the liver mRNAs of an aged DBA/2 mouse, we have cloned and entirel y sequenced the corresponding cDNAs, Both are initiated within the 5' long terminal repeat of a type I Delta 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, T he 6-kb IAP-related transcript corresponds to a post-transcriptional m odification of the 10-kb mRNA, and is generated by a splicing event wi th 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 t o the yeast CCR4 transcription factor at the amino acid level, The spe cific expression of these age-induced transcripts, which account for m ore than 50% of the IAP-related transcripts in the liver of old mice, is therefore entirely consistent with the induction of a single genomi c locus, thus strengthening the importance of position effects for the expression of transposable elements, Characterization of this locus s hould now allow studies on its chromatin and methylation status, and o n the ''molecular factors of senescence'' possibly involved in its ind uction.