Affinage

MAGOH

Protein mago nashi homolog · UniProt P61326

Length
146 aa
Mass
17.2 kDa
Annotated
2026-06-10
26 papers in source corpus 18 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAGOH is a core component of the splicing-dependent exon junction complex (EJC), deposited on mRNAs ~20 nucleotides upstream of exon-exon junctions and retained after nuclear export (PMID:11707413). It functions as an obligate, high-affinity heterodimer with Y14/RBM8A: crystallographic analysis shows MAGOH adopts a flat six-stranded anti-parallel beta sheet that binds the Y14 RNP RNA-binding domain and completely masks its RNA-binding surface, explaining how the EJC achieves stable, sequence-independent association at splice junctions (PMID:10662555, PMID:12781131). This heterodimer is required for EJC incorporation and for downstream post-transcriptional functions including nonsense-mediated mRNA decay (NMD), in which MAGOH is functionally redundant with its paralog MAGOHB — only simultaneous depletion of both impairs NMD (PMID:23917022). Through EJC-dependent control of mRNA fate, MAGOH governs proliferation: in mouse neural stem cells and interneuron progenitors, Magoh dosage controls mitotic spindle integrity and progression, in part by regulating levels of the microcephaly protein Lis1, with haploinsufficiency causing microcephaly via progenitor depletion and p53-dependent apoptosis (PMID:20364144, PMID:31857347). Parallel mitotic requirements are seen in melanoblasts (PMID:23333945). In zebrafish, loss of magoh dysregulates EJC/NMD substrates including foxo3b, and foxo3b loss rescues the resulting motor axon defects, linking the molecular NMD function to organismal phenotype (PMID:32502192). MAGOH also acts beyond canonical EJC roles: it competes with STAT3 for Y14 binding to dampen STAT3 transcriptional activation (PMID:19254694), and its protein stability depends on Y14 heterodimerization and nuclear localization (PMID:30826064).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Established the founding physical interaction of MAGOH, defining its principal binding partner before any complex context was known.

    Evidence Yeast two-hybrid screen and GST pulldown identifying direct RBM8A/Y14 binding

    PMID:10662555

    Open questions at the time
    • Did not place the interaction in a functional complex
    • No structural basis for binding
    • No RNA association demonstrated
  2. 2001 High

    Placed MAGOH within the exon junction complex, showing it is deposited co-transcriptionally upstream of splice junctions and retained through export, defining its role in mRNP marking of spliced transcripts.

    Evidence GST pulldown, reciprocal co-IP, and UV crosslinking/IP of mRNPs in human cells

    PMID:11707413

    Open questions at the time
    • Functional consequence of EJC deposition not yet tested
    • Selectivity for Y14 and TAP over Aly/REF unexplained structurally
  3. 2003 High

    Resolved the structural logic of the MAGOH-Y14 heterodimer, explaining how the EJC achieves sequence-independent, stable mRNA association.

    Evidence X-ray crystallography of the Y14-MAGOH core with biochemical binding validation

    PMID:12781131

    Open questions at the time
    • Structure of the full assembled EJC on RNA not resolved here
    • Did not address how the complex is remodeled or disassembled
  4. 2010 High

    Connected the molecular EJC function to a cell-autonomous role in mitosis, showing Magoh dosage controls cortical neural stem cell division and Lis1 levels, linking it to microcephaly.

    Evidence Mouse haploinsufficiency model with in utero rescue, live imaging and immunofluorescence

    PMID:20364144

    Open questions at the time
    • Mechanism by which Magoh controls Lis1 levels not defined
    • Whether spindle phenotype is EJC/NMD-dependent unresolved
  5. 2013 High

    Demonstrated functional redundancy with the paralog MAGOHB in NMD, showing both incorporate into EJCs and that NMD requires loss of both.

    Evidence siRNA knockdown, RNA immunoprecipitation, and NMD reporter assays in human cells

    PMID:23917022

    Open questions at the time
    • Did not identify endogenous substrate sets distinguishing the paralogs
    • Single lab
  6. 2013 Medium

    Extended the mitotic proliferation role to a second lineage and localized the MAGOH-Y14 complex to the centrosome alongside PLK1, implicating it directly in M-phase machinery.

    Evidence Mouse genetics and melanoma siRNA (melanoblasts); immunostaining and proximity ligation assay (centrosome)

    PMID:23333945 PMID:23949737

    Open questions at the time
    • Centrosomal function inferred, not tested by rescue
    • Link between centrosomal localization and EJC activity unclear
  7. 2009 Medium

    Identified a non-EJC regulatory role: MAGOH competes with STAT3 for Y14 binding to restrain STAT3-driven transcription.

    Evidence Co-immunoprecipitation, siRNA knockdown, and luciferase reporter assays

    PMID:19254694

    Open questions at the time
    • Direct competition not shown by reconstitution
    • Physiological contexts where this operates unknown
  8. 2011 Medium

    Linked Magoh to cell cycle control through Cdk1/Cks regulation, showing the effect depends on Cks introns and thus EJC-dependent mRNA processing.

    Evidence Genetic suppressor screen of a Cdc2 ts mutant, RNAi, and cell cycle analysis

    PMID:21210908

    Open questions at the time
    • Whether regulation is via NMD or splicing not pinned down
    • Single lab
  9. 2014 Medium

    Showed MAGOH binding suppresses Y14 phosphorylation, adding a layer of post-translational regulation to heterodimer assembly.

    Evidence Phos-tag gels, site-directed mutagenesis, in vitro kinase assay, cell-cycle analysis

    PMID:25349214

    Open questions at the time
    • Kinase responsible not definitively identified
    • Functional output of Y14 phosphorylation state unclear
  10. 2019 Medium

    Defined the determinants of MAGOH protein stability, showing it requires Y14 heterodimerization and nuclear localization.

    Evidence Cycloheximide chase, mutagenesis (L136R), immunofluorescence, co-IP

    PMID:30826064

    Open questions at the time
    • Degradation machinery not identified
    • Single lab
  11. 2020 High

    Connected MAGOH's molecular NMD function to organismal phenotype, showing magoh loss dysregulates EJC/NMD substrates including foxo3b, whose removal rescues motor axon defects.

    Evidence Zebrafish homozygous mutants, RNA-seq, and foxo3b loss-of-function genetic epistasis

    PMID:32502192

    Open questions at the time
    • 3'UTR-intron NMD class mechanism not fully resolved
    • Tissue-specific substrate dependence incomplete
  12. 2020 High

    Dissected the dosage- and p53-dependence of Magoh's mitotic function in interneuron progenitors, separating apoptosis (p53-rescuable) from mitotic delay (not rescued in nulls).

    Evidence Conditional Cre-lox knockout, live imaging, transcriptome analysis, p53 genetic epistasis

    PMID:31857347

    Open questions at the time
    • Molecular cause of p53-independent mitotic delay unknown
    • Relevant EJC substrates in interneurons not defined
  13. 2022 Medium

    Mapped distinct MAGOH residues required for Y14 binding versus mRNA association, separating two functional requirements for EJC incorporation.

    Evidence Site-directed mutagenesis (I90T, G18R), co-IP, immunofluorescence, UV-CLIP/RIP

    PMID:35430764

    Open questions at the time
    • Structural basis of G18R mRNA-association defect not resolved
    • Single lab
  14. 2024 Medium

    Identified disease-relevant outputs: MAGOH influences alternative splicing of RON to activate PI3K/AKT in gastric cancer, and EJC depletion perturbs junctional localized translation of Zo-1 and Scrib.

    Evidence RNA pulldown/RIP, RNA-seq, in vivo assays (cancer); siRNA, smFISH, live imaging in Drosophila and human cells (junctions, preprint)

    PMID:38268030

    Open questions at the time
    • Junctional translation role rests on a preprint without MAGOH-specific rescue
    • Direct vs indirect effect on hnRNPA1 not fully separated
  15. 2026 Medium

    Showed individual MAGOH and MAGOHB knockouts retain core EJC function yet cause distinct, non-redundant proliferation and proteome defects.

    Evidence CRISPR/Cas9 knockout, quantitative proteomics, proliferation assays

    PMID:41956154

    Open questions at the time
    • Mechanism linking MAGOH loss to SLC25A4 downregulation unknown
    • Reconciliation with earlier full redundancy claims incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MAGOH's canonical EJC role is mechanistically coupled to its EJC-independent activities (Lis1 control, STAT3 competition, ubiquitin-proteasome association, junctional translation) remains unresolved.
  • No unified model linking mitotic, NMD, and signaling functions
  • EJC-independent isoform (MAGOH-Δ37) function uncharacterized beyond interactome
  • PYM1-mediated EJC destabilization role awaits peer review

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-1640170 Cell Cycle 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
EIF4A3PYM1RBM8ARNPS1STAT3
Complex memberships
exon junction complex (EJC)

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 MAGOH is a component of the splicing-dependent exon-exon junction complex (EJC), binding directly and avidly to Y14 (RBM8A) and TAP (mRNA export factor), but not to other known EJC components such as Aly/REF or RNPS1. MAGOH associates with mRNAs produced by splicing ~20 nucleotides upstream of exon-exon junctions and remains bound after nuclear export. GST pulldown, co-immunoprecipitation, UV crosslinking/immunoprecipitation of mRNPs The EMBO journal High 11707413
2000 MAGOH directly interacts with RBM8A (Y14/RBM8), identified via yeast two-hybrid screen and confirmed by GST fusion protein pulldown assay. Yeast two-hybrid, GST pulldown Genomics High 10662555
2003 High-resolution crystal structure of the Y14-MAGOH core complex reveals that MAGOH has an unusual flat six-stranded anti-parallel beta sheet packed against two helices, and binds with high affinity to the RNP motif RNA-binding domain (RBD) of Y14, completely masking its RNA binding surface, explaining how the EJC maintains stable, RNA sequence-independent association at splice junctions. X-ray crystallography, biochemical binding assays Current biology : CB High 12781131
2010 Magoh controls mouse cerebral cortical size by regulating neural stem cell (NSC) division. Magoh haploinsufficiency causes microcephaly through depletion of intermediate neural progenitors and neuronal apoptosis due to defective mitosis, including disrupted mitotic spindle orientation and integrity, abnormal chromosome number, and genomic instability. A key function of Magoh is to control levels of the microcephaly-associated protein Lis1 during neurogenesis. Mouse genetics (haploinsufficiency model), in utero rescue experiments, live imaging, immunofluorescence Nature neuroscience High 20364144
2013 Both MAGOH and its paralog MAGOHB interact with other EJC core components, incorporate into mRNA-bound EJCs, and activate nonsense-mediated decay (NMD). Simultaneous depletion of MAGOH and MAGOHB, but not individual depletions, impairs NMD in human cells. siRNA knockdown, RNA immunoprecipitation, NMD reporter assays RNA biology High 23917022
2013 MAGOH is required for normal melanoblast development; Magoh haploinsufficiency causes mitotic arrest in melanoblasts and reduction of epidermal (but not dermal) melanoblast populations without increased apoptosis, demonstrating a role in melanoblast proliferation. Mouse genetics, flow cytometry, siRNA knockdown in melanoma cell lines, immunostaining Developmental biology Medium 23333945
2013 RBM8A (Y14) and MAGOH co-localize to the centrosome in human A549 cells (in addition to nuclei), where they form a complex as detected by proximity ligation in situ assay. GFP-PLK1 also co-localizes with RBM8A at centrosomes, implicating the RBM8A-MAGOH complex in M-phase progression via direct centrosomal localization. Immunostaining, proximity ligation in situ assay, fluorescent-tagged protein overexpression Histochemistry and cell biology Medium 23949737
2009 MAGOH inhibits STAT3 transcriptional activation by interfering with the formation of the STAT3-Y14 complex. MAGOH co-immunoprecipitates with Y14, and siRNA-mediated reduction of MAGOH enhances IL-6-induced STAT3 target gene expression. Co-immunoprecipitation, siRNA knockdown, luciferase reporter assay Biochemical and biophysical research communications Medium 19254694
2011 Mouse Magoh is a dosage suppressor of a temperature-sensitive Cdc2 (Cdk1) mutant, and RNAi depletion of Magoh causes cold-sensitive cell cycle defects and synthetic enhancement of the Cdc2 ts phenotype similar to Cks2 depletion. Magoh RNAi causes defects in Cdc2 and Cks protein expression, and these effects are modulated by introns of Cks genes, indicating Magoh regulates Cdk activity through EJC-dependent mRNA processing. Genetic epistasis (suppressor screen), RNAi, cell cycle analysis Genes to cells : devoted to molecular & cellular mechanisms Medium 21210908
2014 MAGOH inhibits phosphorylation of RBM8A (Y14) in vitro and in vivo. Most endogenous RBM8A is phosphorylated (at serine residues 166 and 168) prior to complex formation with MAGOH, and MAGOH binding inhibits further phosphorylation. Phos-tag gel analysis, site-directed mutagenesis, in vitro kinase assay, cell-cycle analysis Experimental biology and medicine (Maywood, N.J.) Medium 25349214
2019 The stability of MAGOH protein depends on its heterodimer formation with Y14 and on nuclear localization: a Magoh L136R mutation that disrupts heterodimer formation causes faster protein degradation. Y14 L118R, which also fails to form heterodimers but retains nuclear localization, is more stable than Magoh L136R, showing nuclear localization provides additional stabilization independent of complex formation. Cycloheximide chase assay, mutagenesis, immunofluorescence, co-immunoprecipitation Biochemical and biophysical research communications Medium 30826064
2020 Homozygous magoh mutations in zebrafish cause muscle disorganization, neural cell death, and motor neuron outgrowth defects, and dysregulate mRNAs subject to EJC-dependent NMD, including a novel class with 3'UTR introns located <50 nt downstream of a stop codon. foxo3b mRNA is an NMD target regulated by the EJC, and loss of foxo3b function in EJC mutant embryos rescues motor axon growth defects. Zebrafish genetics (homozygous mutant), RNA-seq, genetic epistasis (foxo3b loss-of-function rescue) PLoS genetics High 32502192
2020 Conditional Magoh ablation from interneuron progenitors (but not post-mitotic neurons) depletes cortical interneuron number. Magoh deficiency delays progenitor mitotic progression in a dosage-sensitive fashion. p53 ablation in Magoh haploinsufficient progenitors fully rescues apoptosis and interneuron number; in Magoh homozygotes, p53 loss fails to rescue interneuron number or mitotic delay. Conditional knockout (Cre-lox), live imaging, transcriptome analysis, genetic epistasis (p53 ablation) Development (Cambridge, England) High 31857347
2022 Magoh I90T mutation (equivalent to a Drosophila mago nashi mutant) reduces binding to Y14, causing cytoplasmic mislocalization of Magoh and impaired EJC formation. Magoh G18R mutation does not affect Y14 binding but reduces association with spliced mRNAs, also impairing EJC incorporation. Site-directed mutagenesis, co-immunoprecipitation, immunofluorescence, UV crosslinking/RNA immunoprecipitation Genes to cells : devoted to molecular & cellular mechanisms Medium 35430764
2024 MAGOH promotes gastric cancer progression by inhibiting hnRNPA1 expression, which reduces hnRNPA1 binding to RON mRNA, thereby promoting formation of the alternative splice isoform RONΔ160 and activating the PI3K/AKT signaling pathway. RNA pulldown, RNA immunoprecipitation (RIP), RNA-seq, in vitro and in vivo functional assays, siRNA knockdown Journal of experimental & clinical cancer research : CR Medium 38268030
2025 PYM1 binds the RBM8A/MAGOH heterodimer of the EJC core and mediates translation-independent EJC destabilization; EJCs lacking PYM1 interaction show no defect in translation-dependent disassembly but accumulate on non-canonical sites including intronless transcripts or transcripts with fewer and longer exons. CLIP-seq, knockdown, reporter assays, EJC occupancy profiling bioRxivpreprint Medium
2025 MAGOH-Δ37, an alternatively spliced isoform of MAGOH lacking exon 37, does not interact with known EJC proteins (EIF4A3, RBM8A, RNPS1, SAP18), indicating it functions independently of the EJC. Both MAGOH and MAGOH-Δ37 associate with ubiquitin and are upregulated upon proteasomal inhibition, suggesting involvement in the ubiquitin-proteasome system. Co-immunoprecipitation, mass spectrometry interactome capture, proteasome inhibitor treatment Biochemical and biophysical research communications Medium 40889427
2026 Individual knockout of MAGOH or MAGOHB each maintains core EJC functions but causes significant growth defects, demonstrating non-redundant roles in proliferation. MAGOH loss uniquely downregulates the mitochondrial ADP/ATP carrier SLC25A4, while MAGOHB loss specifically impairs PI3K-Akt signaling. CRISPR/Cas9 knockout, quantitative proteomics, cell proliferation assays Biochimica et biophysica acta. Gene regulatory mechanisms Medium 41956154
2024 Depletion of MAGOH (an EJC core component) perturbs junctional distribution and localized translation of Zo-1 and Scrib mRNAs at cell-cell junctions, as well as junctional accumulation of their protein products, implicating MAGOH in localizing specific mRNAs for translation at epithelial cell junctions. siRNA knockdown, smFISH, live imaging, epithelial cell polarity assays in Drosophila and human cells bioRxivpreprint Low
2016 MAGOH and MAGOHB knockdown in melanoma cells decreases NMD activity, leading to upregulation of the pro-apoptotic protein GADD45A and subsequent apoptosis. The effect on apoptosis is enhanced by simultaneous knockdown of both paralogs. siRNA knockdown, NMD reporter assay, flow cytometry, Western blot Cells Medium 36497117

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex. The EMBO journal 182 11707413
2010 The exon junction complex component Magoh controls brain size by regulating neural stem cell division. Nature neuroscience 150 20364144
2003 Structure of the Y14-Magoh core of the exon junction complex. Current biology : CB 104 12781131
2000 MAGOH interacts with a novel RNA-binding protein. Genomics 62 10662555
2013 Two mammalian MAGOH genes contribute to exon junction complex composition and nonsense-mediated decay. RNA biology 48 23917022
2013 The EJC component Magoh regulates proliferation and expansion of neural crest-derived melanocytes. Developmental biology 35 23333945
2013 RNA-binding protein RBM8A (Y14) and MAGOH localize to centrosome in human A549 cells. Histochemistry and cell biology 25 23949737
2009 The exon-junction complex proteins, Y14 and MAGOH regulate STAT3 activation. Biochemical and biophysical research communications 23 19254694
2020 Zebrafish rbm8a and magoh mutants reveal EJC developmental functions and new 3'UTR intron-containing NMD targets. PLoS genetics 22 32502192
2014 Generation of a Magoh conditional allele in mice. Genesis (New York, N.Y. : 2000) 21 24771530
2020 MAGOH/MAGOHB Inhibits the Tumorigenesis of Gastric Cancer via Inactivation of b-RAF/MEK/ERK Signaling. OncoTargets and therapy 19 33328743
2020 Dosage-dependent requirements of Magoh for cortical interneuron generation and survival. Development (Cambridge, England) 16 31857347
2011 Genetic analyses using a mouse cell cycle mutant identifies magoh as a novel gene involved in Cdk regulation. Genes to cells : devoted to molecular & cellular mechanisms 15 21210908
2024 MAGOH promotes gastric cancer progression via hnRNPA1 expression inhibition-mediated RONΔ160/PI3K/AKT signaling pathway activation. Journal of experimental & clinical cancer research : CR 11 38268030
2014 Phosphorylation status of human RNA-binding protein 8A in cells and its inhibitory regulation by Magoh. Experimental biology and medicine (Maywood, N.J.) 11 25349214
2022 Exon-dependent transcriptional adaptation by exon-junction complex proteins Y14/RNP-4 and MAGOH/MAG-1 in Caenorhabditis elegans. PLoS genetics 8 36315586
2022 MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A. Cells 8 36497117
2023 The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes. RNA biology 7 37294214
2019 The stability of Magoh and Y14 depends on their heterodimer formation and nuclear localization. Biochemical and biophysical research communications 6 30826064
2024 Upregulation of Long Noncoding RNA MAGOH-DT Mediates TNF-α and High Glucose-Induced Endothelial-Mesenchymal Transition in Arteriosclerosis Obliterans. The Tohoku journal of experimental medicine 4 38811212
2022 Mutations equivalent to Drosophila mago nashi mutants imply reduction of Magoh protein incorporation into exon junction complex. Genes to cells : devoted to molecular & cellular mechanisms 3 35430764
2020 Development of Magoh protein-overexpressing HEK cells for optimized therapeutic protein production. Biotechnology and applied biochemistry 3 32249976
2025 Pan-cancer analysis of oncogenic role of MAGOH and experiment validation in hepatocellular carcinoma. Scientific reports 1 40596687
2025 An EJC-independent novel isoform of MAGOH: the MAGOH-Δ37 isoform and its interactome capture. Biochemical and biophysical research communications 1 40889427
2026 Proteomic analysis reveals distinct gene regulatory functions of the paralogs MAGOH and MAGOHB in cell proliferation. Biochimica et biophysica acta. Gene regulatory mechanisms 0 41956154
2020 The EJC component Magoh in non-vertebrate chordates. Development genes and evolution 0 32632492

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