Structure and Expression of the TREX1 and TREX2 3′→5′ Exonuclease Genes

Abstract

The TREX1 and TREX2 genes encode mammalian 3'-->5' exonucleases. Expression of the TREX genes in human cells was investigated using a reverse transcription-polymerase chain reaction strategy. Our results show that TREX1 and TREX2 are expressed in all tissues tested, providing direct evidence for the expression of these genes in human cells. Potential transcription start sites are identified for the TREX genes using rapid amplification of cDNA ends to recover the 5'-flanking regions of the TREX transcripts. The 5'-flanking sequences indicate transcription initiation from consensus putative promoters identified -140 and -650 base pairs upstream of the TREX1 open reading frame (ORF) and -623 and -753 base pairs upstream of the TREX2 ORF. Novel TREX1 and TREX2 cDNAs are identified that contain protein-coding sequences generated from exons positioned in genomic DNA up to 18 kilobases 5' to the TREX1 ORF and up to 25 kilobases 5' to the TREX2 ORF. These novel cDNAs and sequences in the GenBank data base indicate that transcripts containing the TREX1 and TREX2 ORFs are produced using a variety of mechanisms that include alternate promoter usage, alternative splicing, and varied sites for 3' cleavage and polyadenylation. These initial studies have revealed previously unrecognized complexities in the structure and expression of the TREX1 and TREX2 genes.