Genomic Structure and 5′-Flanking Sequences of RatN-Acetylglucosaminyltransferase I Gene and Regulatory Role of Its Transcriptional Diversity

It has been known that mouse, rat, and human N-acetylglucosaminyltransferase I (GnT-I) genes produce at least two transcripts, which differ in their 5'-untranslated region (5'-UTR) length, and the longer transcript is preferentially expressed in brains. However, the physiological meaning of this brain-specific expression pattern was unknown. We cloned the rat GnT-I gene and analyzed its structure. It consisted of five exons, and four of them coded only 5'-UTRs. A putative NF-kappaB binding site was found in the 5'-flanking sequence for the transcript that was previously shown to be induced by inflammation. The unusually long 5'-UTR of the major GnT-I transcript in rat brain was shown to inhibit protein production from the following coding sequence in COS7 cells. Comparison of the GnT-I protein/mRNA ratio in rat brain and liver showed that GnT-I mRNA in the brain was translated 3.8-times less efficiently than in the liver. Implications are discussed of these results in regulation of GnT-I expression in rat brain.