STRUCTURE AND ORGANIZATION OF THE HUMAN NEURONATIN GENE

Neuronatin is a brain-specific human gene that we recently isolated an d observed to be selectively expressed during brain development. In th is report, the genomic structure and organization of human neuronatin is described, The human gene spans 3973 bases and contains three exons and two introns. Based on primer extension analysis, a single cap sit e is located 124 bases upstream from the methionine (ATG) initiation c odon, in good context, GAACCATGG. The promoter contains a modified TAT A box, CATAAA (-27), and a modified CAAT box, GGCGAAT (-59). The 5'-fl anking region contains putative transcription factor binding sites for SP-1, AP-2 (two sites), delta-subunit, SRE-2, NF-A1, and ETS. In addi tion, a 21-base sequence highly homologous to the neural restrictive s ilence element that governs neuron-specific gene expression is observe d at -421. Furthermore, SP-1 and AP-3 binding sites are present in int ron 1. All splice donor and acceptor sites conformed to the GT/AG rule . Exon 1 encodes 24 amino acids, exon 2 encodes 27 amino acids, and ex on 3 encodes 30 amino acids. At the 3'-end of the gene, the poly(A) si gnal, AATAAA, poly(A) site, and GT cluster are observed. The neuronati n gene is expressed as two mRNA species, alpha and beta, generated by alternative splicing. The alpha-form contains all three exons, whereas in the beta-form, the middle exon has been spliced out. The third nuc leotide of all frequently used codons, except threonine, of neuronatin is either G or C, consistent with codon usage expected for Homo sapie ns. This information about the structure of the human neuronatin gene will help in understanding the significance of this gene in brain deve lopment and human disease. (C) 1996 Academic Press, Inc.