Organization and expression of mouse repetitive DNA sequences

Abstract

Interspersed repetitive DNA sequences comprise 10-30% of mammalian genomes. To understand what functions these sequences may have, the organization and expression of four non-Alu mouse repetitive DNA sequences families was investigated. The Alu family was included in our transcriptional studies. Two of these families, Bam5 and R, are present at 5 {dollar}\times{dollar} 10{dollar}\sp4{dollar} and 10{dollar}\sp5{dollar} copies per genome respectively and are part of the L1Md long interspersed repetitive sequence family. Two newly isolated families, LLRep1 and LLRep3, are present at 14,000 and 200 copies per genome respectively. All four families have analogous counterparts in the human genome. Bam5, R and LLRep1 seem to be non-randomly distributed in the genome in that they flank known structural genes more often than randomly selected clones.;All four non-Alu families are transcribed by RNA polymerase II. Bam5 and R transcripts probably result from read-through from adjacent structural genes. LLRep1 exhibits an asymmetric pattern of hybridization to nuclear RNA, suggesting that members of this family may have their own promoters or are generally oriented in only one direction relative to transcription units. About 80% of Alu family transcripts result from read-through from adjacent structural gene promoters where they are asymmetrically transcribed. 20% of Alu members are discrete RNA polymerase III products.;Although the expression of the four repetitive families does not appear to be developmentally-regulated or tissue-specific, there is an overall increased level of expression in embryonic tissue and tissue culture RNA as compared to adult tissue RNA.;LLRep3's characteristics suggest its evolution from a structural gene into a repeated sequence family. LLRep3 DNA hybridizes to a discrete 1-1.5 kb transcript in poly(A){dollar}\sp+{dollar} RNA in all mouse cell lines and tissues examined. Sequence analysis of two cDNAs and a genomic member of this family indicates the presence of an open reading frame. LLRep3 is evolutionarily conserved in the chicken genome as a non-repetitive element which is heavily transcribed into a discrete poly(A){dollar}\sp+{dollar} transcript. These observations suggest that LLRep3 may have arisen by retroposition and the family may represent a collection of pseudogenes with a functional gene amongst them.