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

被引:44
|
作者
Salicioni, AM
Xi, MR
Vanderveer, LA
Balsara, B
Testa, JR
Dunbrack, RL
Godwin, AK
机构
[1] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA
[2] Fox Chase Canc Ctr, Human Genet Program, Philadelphia, PA 19111 USA
[3] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA
[4] W China Univ Med Sci, Chengdu 610041, Sichuan Provinc, Peoples R China
关键词
D O I
10.1006/geno.2000.6315
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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. (C) 2000 Academic Press.
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页码:54 / 62
页数:9
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