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

Abstract

  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-κB 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.