Structural and functional characterization of the human gene for sorting nexin 1 (SNX1)

The aim of the present study was to identify the gene for sorting nexin 1 ( SNX1) to evaluate the potential for tissue-specific alternative splicing an d to analyze the activity of the SNX1 promoter. The coding DNA for SNX1 was divided between 15 exons in 43 kb of genomic DNA located on human chromoso me 15q22, Although SNX1 mRNA expression was widespread in human tissues, al ternative splicing is thought to generate skipped exons in SNX1 cDNAs. By d etermination of the SNX1 gene structure and an analysis of the mRNAs in a v ariety of tissues using RT-PCR, we demonstrated that SNX1 mRNAs are alterna tively spliced, Exon-skipped products were less abundant than full-length S NX1 mRNA species, but the ratio of skipped to full-length mRNA indicated th at alternative splicing may be developmentally regulated in the liver. Cons istent with widespread mRNA expression, the SNX1 promoter was GC rich and l acked a TATA box, features characteristic of housekeeping promoters. The pr omoter activity was dependent on the presence of proximal sequences that co ntained initiator elements and predicted binding sites for the transcriptio n factors Spl and E2F, These findings indicate that regulation of SNX1 gene expression at the transcriptional level is likely minor. Rather, developme ntally specific exon skipping provides a potential mechanism for regulating the activity of SNX1.