Structure and expression of the TREX1 and TREX2 3 '-> 5 ' exonuclease genes

The TREX1 and TREX2 genes encode mammalian 3'-->5' exonucleases. Expression of the TREX genes in human cells was investigated using a reverse transcri ption-polymerase chain reaction strategy. Our results show that TREX1 and T REX2 are expressed in all tissues tested, providing direct evidence for the expression of these genes in human cells. Potential transcription start si tes are identified for the TREX genes using rapid amplification of cDNA end s to recover the 5'-flanking regions of the TREX transcripts. The 5'-flanki ng sequences indicate transcription initiation from consensus putative prom oters identified -140 and -650 base pairs upstream of the TREX1 open readin g 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 th e TREX1 ORF and up to 25 kilobases 5' to the TREX2 ORF. These novel cDNAs a nd sequences in the GenBank(TM) data base indicate that transcripts contain ing the TREX1 and TREX2 ORFs are produced using a variety of mechanisms tha t include alternate promoter usage, alternative splicing, and varied sites for 3' cleavage and polyadenylation. These initial studies have revealed pr eviously unrecognized complexities in the structure and expression of the T REX1 and TREX2 genes.