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 gene at chromosome 17p13.3. To help determine the function(s) of OVCA1, we used a yeast two-hybrid screening approach to identify OVCA1-associating proteins. 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 member of a highly conserved RNA-binding motif (RBM) protein family that is highly conserved evolutionarily. Northern blot analysis revealed that BOV-1 is ubiquitously expressed and that three distinct messenger RNA species are expressed, 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, spleen, 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 determined that the gene coding the 1- and the 3.2-kb transcripts (HGMW-approved gene symbol RBM8A) maps to 14q22-q23, whereas a second highly related gene coding for the 5.8-kb transcript resides at chromosome 5q13-q14 (HGMW-approved gene symbol RBM8B). The predicted proteins encoded by RBM8A and RBM8B are identical except that RBM8B is 16 amino acids shorter at its N-terminus. Molecular modeling of the RNA-binding domain of RBM8A and RBM8B, based on homology to the sex-lethal protein of Drosophila, identifies conserved residues in the RBM8 protein family that are likely to contact RNA in a protein-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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, COS Cells, Chromosome Mapping, Chromosomes, Human, Pair 14, Chromosomes, Human, Pair 5, Cloning, Molecular, Conserved Sequence, DNA, Complementary, Female, Gene Expression, Genes, Tumor Suppressor, Humans, In Situ Hybridization, Fluorescence, Male, Microscopy, Fluorescence, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Isoforms, Protein Structure, Tertiary, Proteins, RNA, Messenger, RNA-Binding Proteins, Sequence Alignment, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Tissue Distribution, Tumor Suppressor Proteins
Genomics
Date: Oct. 01, 2000
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