Identification and structural analysis of human RBM8A and RBM8B: Two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor

The OVCA1 gene is a candidate for the breast and ovarian tumor suppressor g ene at chromosome 17p13.3. To help determine the function(s) of OVCA1, we u sed a yeast two-hybrid screening approach to identify OVCA1-associating pro teins. One such protein, which we initially referred to as BOV-1 (binder of OVCA1-1) is 173 or 174 amino acids in length and appears to be a new membe r of a highly conserved RNA-binding motif (RBM) protein family that is high ly conserved evolutionarily. Northern blot analysis revealed that BOV-1 is ubiquitously expressed and that three distinct messenger RNA species are ex pressed, 1-, 3.2-, and 5,8-kb transcripts. The 1-kb transcript is the most abundant and is expressed at high levels in the testis, heart, placenta, sp leen, thymus, and lymphocytes. Using fluorescence in situ hybridization and the 5,8-kb complementary DNA probe, we determined that BOV-1 maps to both chromosome 5q13-q14 and chromosome 14q22-q23, Further sequence analysis det ermined that the gene coding the 1- and the 3,2-kb transcripts (HGMW-approv ed gene symbol RBM8A) maps to 14q22-q23, whereas a second highly related ge ne coding for the 5,8-kb transcript resides at chromosome 5q13-q14 (HGMW-ap proved gene symbol RBM8B). The predicted proteins encoded by RBM8A and RBM8 B are identical except that RBM8B is 16 amino acids shorter at its N-termin us. Molecular modeling of the RNA-binding domain of RBM8A and RBM8B, based on homology to the sex-lethal protein of Drosophila, identifies conserved r esidues in the RBM8 protein family that are likely to contact RNA in a prot ein-RNA complex, The conservation of sequence and structure through such an evolutionarily divergent group of organisms suggests an important function for the RBM8 family of proteins. (C) 2000 Academic Press.