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Gene Review

RBM8A  -  RNA binding motif protein 8A

Homo sapiens

Synonyms: BOV-1, BOV-1A, BOV-1B, BOV-1C, Binder of OVCA1-1, ...
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Disease relevance of RBM8A

  • Our results suggest major differences in the interactions of SIVmac251 and macrophage-tropic HIV-1 isolates with 19, N13, and Y14 in the amino terminus; with Q93 in extracellular loop 1; and with extracellular loop 2 of human CCR5 [1].

High impact information on RBM8A

  • Like Y14 and Aly/REF, hUpf3 binds to spliced mRNAs specifically ( approximately 20 nucleotides) upstream of exon-exon junctions [2].
  • In contrast, REF/Aly, Y14, and Magoh remain stably bound to spliced mRNA, indicating that these three proteins are components of the EJC core [3].
  • Nonetheless, hUpf2 is necessary for NMD mediated by tethered Y14 [4].
  • Interestingly, Y14 associates preferentially with mRNAs produced by splicing but not with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs [5].
  • We describe a novel RNA binding protein, Y14, a predominantly nuclear nucleocytoplasmic shuttling protein [5].

Biological context of RBM8A


Anatomical context of RBM8A

  • Here, using microinjection of pre-mRNAs into Xenopus oocyte nuclei followed by immunoprecipitation of RNase-fragmented mRNAs from the cytoplasm, we show that Y14 is stably bound to sequences immediately upstream of exon-exon junctions [9].
  • Also similar to MAGOH, RBM8 expression is serum inducible in quiescent NIH3T3 fibroblast cells [10].
  • How Y14 and other components of the EJC are removed from mRNAs into the cytoplasm has not been determined.RESULTS: We show that Y14 but not another EJC component, Aly/REF, is present in polysome profile fractions containing one ribosome per mRNA [11].
  • Staufen-1, Y14, Mago-m, and Pumilio-1 were expressed in intestinal epithelial cells of both villus and crypt and in Caco-2 and IEC-6 cells [12].

Associations of RBM8A with chemical compounds

  • We have cloned and characterized two genomic loci encoding the human type II gonadotropin-releasing hormone (GnRH) receptor and RNA-binding motif protein-8 (RBM8A) [7].
  • Y14 linked to the COOH terminus of yellow fluorescent protein (YFP; YC-Y14), and NXF1 fused to the NH2 terminus of YFP (YN-NXF1) expressed in MCF7 cells yielded BiFC upon specific binding [13].
  • Moreover, we found that Y14 is possibly methylated at multiple arginine residues in the carboxyl-terminal domain and that methylation of Y14 was antagonized by phosphorylation of RS dipeptides [14].
  • This requires the juxtamembrane tyrosine Y1001 (Y2) of Met, but not the multifunctional docking site (Y14/15) or any additional C-terminal tyrosine residues (Y13-16) [15].
  • This binding surface largely overlaps with the dimer interface and is strongly positively charged, providing a rationale for the exclusive binding of the monomer to the peptide and the requirement of the negative sulfate groups at the Y10 and Y14 side-chains [16].

Physical interactions of RBM8A

  • Magoh binds avidly and directly to Y14 and TAP, but not to other known components of the complex, and is found in Y14-containing mRNPs in vivo [17].
  • Y14 is part of a multi-protein complex that also contains the mRNA export factor TAP [9].

Other interactions of RBM8A


Analytical, diagnostic and therapeutic context of RBM8A

  • 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 [21].
  • 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 [21].
  • In contrast, Y14 and magoh, which remain stably associated with mRNA after export to the cytoplasm, join the EJC during or after completion of exon-exon ligation [22].
  • 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) [21].


  1. Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses. Kuhmann, S.E., Platt, E.J., Kozak, S.L., Kabat, D. J. Virol. (1997) [Pubmed]
  2. Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex. Kim, V.N., Kataoka, N., Dreyfuss, G. Science (2001) [Pubmed]
  3. 5' exon interactions within the human spliceosome establish a framework for exon junction complex structure and assembly. Reichert, V.L., Le Hir, H., Jurica, M.S., Moore, M.J. Genes Dev. (2002) [Pubmed]
  4. Y14 and hUpf3b form an NMD-activating complex. Gehring, N.H., Neu-Yilik, G., Schell, T., Hentze, M.W., Kulozik, A.E. Mol. Cell (2003) [Pubmed]
  5. Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm. Kataoka, N., Yong, J., Kim, V.N., Velazquez, F., Perkinson, R.A., Wang, F., Dreyfuss, G. Mol. Cell (2000) [Pubmed]
  6. A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12. Morgan, K., Conklin, D., Pawson, A.J., Sellar, R., Ott, T.R., Millar, R.P. Endocrinology (2003) [Pubmed]
  7. The genes encoding the type II gonadotropin-releasing hormone receptor and the ribonucleoprotein RBM8A in humans overlap in two genomic loci. Faurholm, B., Millar, R.P., Katz, A.A. Genomics (2001) [Pubmed]
  8. Conserved physical linkage of GnRH-R and RBM8 in the medaka and human genomes. Okubo, K., Mitani, H., Naruse, K., Kondo, M., Shima, A., Tanaka, M., Aida, K. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  9. The Y14 protein communicates to the cytoplasm the position of exon-exon junctions. Kim, V.N., Yong, J., Kataoka, N., Abel, L., Diem, M.D., Dreyfuss, G. EMBO J. (2001) [Pubmed]
  10. MAGOH interacts with a novel RNA-binding protein. Zhao, X.F., Nowak, N.J., Shows, T.B., Aplan, P.D. Genomics (2000) [Pubmed]
  11. Translation is required to remove Y14 from mRNAs in the cytoplasm. Dostie, J., Dreyfuss, G. Curr. Biol. (2002) [Pubmed]
  12. Developmental and regional expression and localization of mRNAs encoding proteins involved in RNA translocation. Islam, S., Montgomery, R.K., Fialkovich, J.J., Grand, R.J. J. Histochem. Cytochem. (2005) [Pubmed]
  13. In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains. Schmidt, U., Richter, K., Berger, A.B., Lichter, P. J. Cell Biol. (2006) [Pubmed]
  14. Phosphorylation of Y14 modulates its interaction with proteins involved in mRNA metabolism and influences its methylation. Hsu, I.a.W., Hsu, M., Li, C., Chuang, T.W., Lin, R.I., Tarn, W.Y. J. Biol. Chem. (2005) [Pubmed]
  15. c-Cbl is involved in Met signaling in B cells and mediates hepatocyte growth factor-induced receptor ubiquitination. Taher, T.E., Tjin, E.P., Beuling, E.A., Borst, J., Spaargaren, M., Pals, S.T. J. Immunol. (2002) [Pubmed]
  16. Recognition of RANTES by Extracellular Parts of the CCR5 Receptor. Duma, L., H??ussinger, D., Rogowski, M., Lusso, P., Grzesiek, S. J. Mol. Biol. (2007) [Pubmed]
  17. Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex. Kataoka, N., Diem, M.D., Kim, V.N., Yong, J., Dreyfuss, G. EMBO J. (2001) [Pubmed]
  18. Sheep exhibit novel variations in the organization of the mammalian type II gonadotropin-releasing hormone receptor gene. Gault, P.M., Morgan, K., Pawson, A.J., Millar, R.P., Lincoln, G.A. Endocrinology (2004) [Pubmed]
  19. The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Ballut, L., Marchadier, B., Baguet, A., Tomasetto, C., Séraphin, B., Le Hir, H. Nat. Struct. Mol. Biol. (2005) [Pubmed]
  20. eIF4A3 is a novel component of the exon junction complex. Chan, C.C., Dostie, J., Diem, M.D., Feng, W., Mann, M., Rappsilber, J., Dreyfuss, G. RNA (2004) [Pubmed]
  21. Identification and structural analysis of human RBM8A and RBM8B: two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor. Salicioni, A.M., Xi, M., Vanderveer, L.A., Balsara, B., Testa, J.R., Dunbrack, R.L., Godwin, A.K. Genomics (2000) [Pubmed]
  22. A simple whole cell lysate system for in vitro splicing reveals a stepwise assembly of the exon-exon junction complex. Kataoka, N., Dreyfuss, G. J. Biol. Chem. (2004) [Pubmed]
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