An expressed GNRP-like gene shares a bi-directional promoter with SF3A2 (SAP62) immediately upstream of AMH

A region of homology, containing the contiguous SF3A2 (formerly called SAP6 2) and AMH genes, exists between human chromosome 19 (HSA19p) and mouse chr omosome 10 (MNU10). In a previous study it was shown that SF3A2/Sf3a2 is ve ry highly conserved between the two species and that AMH/Amh is somewhat le ss conserved although both human and mouse genes encode a protein (AMH) pla ying the same critical role during early male sex differentiation. The clos e association between SF3a2/Sf3a2 and AMH/Amh was thought to maintain open chromatin in the AMH/Amh promoter region, thus facilitating the necessary p recise timing of AMH/Amh expression following that of SRY/Sry at the onset of testis differentiation. Further investigation of DNA upstream of Amh has revealed that there is another gene, in close association (about 400 bp) w ith Sf3a2, which has significant similarities to the N-terminus of a known guanine nucleotide releasing protein (GNRP) and consequently is provisional ly named GNRPx/Gnrpx. The Gnrpx-SPa2-Amh (GSA) locus of the mouse (MMU10) i s conserved in the human (HSA19p). Mapping the Sf3a2 transcription start si te eventually led us to locate and characterize its promoter. We. found tha t Sf3a2 and Gnrpx share a bi-directional promoter, with the latter being tr anscribed in an antisense direction. It has now been shown by RT-PCR analys is that both Sf3a2 and Gnrpx are widely expressed and therefore are likely to be. 'housekeeping' genes. GNRPx/Gnrpx messenger RNA codes for a C-termin ally truncated protein (149/164 aa), which contains an as yet uncharacteriz ed domain common to GNRPs (and related proteins) and which may therefore ac t as a specific antagonist of a complete GNRP protein (> 1200 aa) involved in the regulation of the GTPase (G-protein/Ras) cycle. (C) 2001 Elsevier Sc ience B.V. All rights reserved.