NF1 gene: Promoter, 5′ UTR, and 3′ UTR

Abstract

The NF1 gene has a TATA-less promoter with a classic CpG island and a 454-bp 5′ untranslated region (UTR). The CpG island is normally unmethylated, with the gene actively transcribed in all tissues examined to date. Although there are no known NF1-causative mutations within the promoter or 5′ UTR, there are reported polymorphisms and rare variants. Some functional analyses and bioinformatic predictions of the promoter and 5′ UTR have been performed, but these regions are not yet extensively characterized. These regulatory sequences are very highly conserved in rodent orthologs, although the upstream gene sequences diverge from the human locus. Very recently, a microRNA locus (miR-4733) was identified 500-bp upstream of the NF1 transcription start site, encoded on the opposite strand. This raises the specter of co-regulation, but that remains to be investigated. The NF1 3′ untranslated region is quite large (3.5 kb) with two polyadenylation sites. The functional significance of (and utility of) these alternative 3′ ends is not known. As with the promoter, there are no known disease-causing mutations in the 3′ UTR. This region has not yet been functionally characterized to identify regulatory sequences, although one microRNA (miR-10b) was found to regulate the NF1 transcript via the 3′ UTR.