HUMAN ARHGDIG, A GDP-DISSOCIATION INHIBITOR FOR RHO-PROTEINS - GENOMIC STRUCTURE, SEQUENCE, EXPRESSION ANALYSIS, AND MAPPING TO CHROMOSOME 16P13.3

GDP-dissociation inhibitors (GDIs) play a primary role in modulating t he activity of GTPases. We recently reported the identification of a n ew GDI for the Rho-related GTPases named RhoGDI gamma. This gene is no w designated ARHGDIG; by HUGO. Here, in a detailed analysis of tissue expression of ARHGDIG, we observe high levels in the entire brain, wit h regional variations. The mRNA is also present at high levels in kidn ey and pancreas and at moderate levels in spinal cord, stomach, and pi tuitary gland. In other tissues examined, the mRNA levels are very low (lung, trachea, small intestine, colon, placenta) or undetectable. RT -PCR analysis of total RNA isolated from exocrine pancreas and islets shows that the gene is expressed in both tissues. We also report the g enomic structure of ARHGDIG. The gene spans over 4 kb and is organized into six exons and live introns. The upstream region lacks a canonica l TATA box and contains several putative binding sites for ubiquitous and tissue-specific factors active in central nervous system developme nt. Using FISH, we have mapped the gene to chromosome band 16p13.3. Th is band is rich in deletion mutants of genes involved in several human diseases, notably polycystic kidney disease, alpha-thalassemia, tuber ous sclerosis, mental retardation, and cancer. The promoter structure and the chromosomal location of RhoGDI gamma suggest its importance an d underscore the need for further investigation into its biology. (C) 1998 Academic Press.