Alternative titles; symbols
HGNC Approved Gene Symbol: MAGOH
Cytogenetic location: 1p32.3 Genomic coordinates (GRCh38): 1:53,226,900-53,238,518 (from NCBI)
MAGOH interacts with a component of the mammalian exon junction complex (EJC) and functions in the nonsense-mediated mRNA decay (NMD) pathway (Singh et al., 2013).
Drosophila that have mutations in their mago nashi (grandchildless) gene have a 'grandchildless' phenotype, a result of producing progeny with defects in germplasm assembly and germline development. Zhao et al. (1998) cloned a cDNA that appears to encode a human homolog of mago nashi (MAGOH) from a human fetal brain cDNA library. The predicted 146-amino acid MAGOH protein is 90% identical to Drosophila mago nashi. Zhao et al. (1998) also identified a cDNA encoding the mouse MAGOH homolog. The predicted mouse and human MAGOH proteins are 100% identical. Northern blot analysis revealed that MAGOH is expressed ubiquitously in adult human tissues. The expression of mouse Magoh in quiescent fibroblasts was induced by serum stimulation.
By database searching, Singh et al. (2013) showed that the human MAGOH gene encodes a protein of 146 amino acids. A second MAGOH gene, MAGOHB (619552), and 2 MAGOH pseudogenes were also identified. MAGOHB is 2 amino acids longer than MAGOH, but the MAGOH and MAGOHB proteins are otherwise identical except for their first 3 residues. Phylogenetic analysis indicated that the MAGOHB gene was an evolutionarily conserved ortholog of MAGOH, and that the 2 genes evolved from a common ancestor after a gene duplication event. The existence of duplicated MAGOH genes was restricted to the mammalian clade. Quantitative RT-PCR analysis showed that the Magoh and MagohB genes are ubiquitously expressed in mouse tissues. Expression of Magoh and MagohB in lipopolysaccharide (LPS)-stimulated mouse macrophages indicated that the 2 genes are differentially regulated under physiologic conditions at the transcriptional level. MAGOH and MAGOHB were expressed in HEK293 and HeLa cell lines, and the expression was likely regulated in a cell type-specific manner.
Using radiation hybrid panels, Zhao et al. (1998) mapped the MAGOH gene to chromosome 1p34-p33 and the mouse Magoh gene near position 51 on chromosome 4.
Stumpf (2021) mapped the MAGOH gene to chromosome 1p32.3 based on an alignment of the MAGOH sequence (GenBank BC018211) with the genomic sequence (GRCh38).
Palacios et al. (2004) demonstrated that the translation initiation factor EIF4A3 (608546) interacts with Barentsz (MLN51; 606504) and is a component of the oskar messenger RNP localization complex. Moreover, EIF4A3 interacts with Mago-Y14 and thus provides the molecular link between Barentsz and the heterodimer. The mammalian Mago (also known as Magoh)-Y14 (605313) heterodimer is a component of the exon junction complex. The exon junction complex is deposited on spliced mRNAs and functions in nonsense-mediated mRNA decay (NMD), a surveillance mechanism that degrades mRNAs with premature translation termination codons. Palacios et al. (2004) showed that both Barentsz and EIF4A3 are essential for NMD in human cells. Thus, Palacios et al. (2004) concluded that they identified EIF4A3 and Barentsz as components of a conserved protein complex that is essential for mRNA localization in flies and NMD in mammals.
Oskar mRNA localization at the posterior pole of the Drosophila oocyte is essential for germline and abdomen formation in the future embryo. Y14/RBM8 and MAGOH, human homologs of nuclear shuttling proteins required for oskar mRNA localization, are core components of the exon-exon junction complex (EJC). The EJC is deposited on mRNAs in a splicing-dependent manner, 20 to 24 nucleotides upstream of exon-exon junctions, independent of the RNA sequence. This indicates a possible role of splicing in oskar mRNA localization, challenging the established notion that the oskar 3-prime untranslated region is sufficient for this process. Oskar mRNA localization at the posterior pole of the Drosophila oocyte is essential for germline and abdomen formation in the future embryo. Hachet and Ephrussi (2004) demonstrated that splicing at the first exon-exon junction of oskar RNA is essential for oskar mRNA localization at the posterior pole. They revisited the issue of sufficiency of the oskar 3-prime untranslated region for posterior localization and showed that the localization of unrelated transcripts bearing the oskar 3-prime untranslated region is mediated by endogenous mRNA. Hachet and Ephrussi (2004) concluded that their results reveal an important new function for splicing: regulation of messenger ribonucleoprotein complex assembly and organization for mRNA cytoplasmic localization.
Using immunoprecipitation in transfected HeLa cells, Singh et al. (2013) found that both MAGOH and MAGOHB interacted with Y14 (RBM8A; 605313), a core component of the EJC, to form heterodimers, and were efficiently incorporated into EJCs assembled during splicing. Tethering experiments revealed that both MAGOH proteins operated in the NMD pathway and recruited NMD-activating factors to the 3-prime UTR of a tethering reporter mRNA with similar efficiency. Knockdown analysis further indicated that MAGOH and MAGOHB collectively supported NMD.
Hachet, O., Ephrussi, A. Splicing of oskar RNA in the nucleus is coupled to its cytoplasmic localization. Nature 428: 959-963, 2004. [PubMed: 15118729] [Full Text: https://doi.org/10.1038/nature02521]
Palacios, I. M., Gatfield, D., St Johnston, D., Izaurralde, E. An eIF4AIII-containing complex required for mRNA localization and nonsense-mediated mRNA decay. Nature 427: 753-757, 2004. [PubMed: 14973490] [Full Text: https://doi.org/10.1038/nature02351]
Singh, K. K., Wachsmuth, L., Kulozik, A. E., Gehring, N. H. Two mammalian MAGOH genes contribute to exon junction complex composition and nonsense-mediated decay. RNA Biol. 10: 1291-1298, 2013. [PubMed: 23917022] [Full Text: https://doi.org/10.4161/rna.25827]
Stumpf, A. M. Personal Communication. Baltimore, Md. 05/06/2021.
Zhao, X.-F., Colaizzo-Anas, T., Nowak, N. J., Shows, T. B., Elliott, R. W., Aplan, P. D. The mammalian homologue of mago nashi encodes a serum-inducible protein. Genomics 47: 319-322, 1998. [PubMed: 9479507] [Full Text: https://doi.org/10.1006/geno.1997.5126]