Affinage

RBM8A

RNA-binding protein 8A · UniProt Q9Y5S9

Length
174 aa
Mass
19.9 kDa
Annotated
2026-04-28
70 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM8A (Y14) is a core subunit of the exon junction complex (EJC) that coordinates post-transcriptional mRNA fate — including nonsense-mediated decay, mRNA stabilization, translational enhancement, and alternative splicing — while also functioning outside the EJC in DNA repair and signal transduction. Y14 binds spliced mRNAs immediately upstream of exon–exon junctions and remains associated until displaced by translating ribosomes; its atypical RRM domain engages Magoh in a stable heterodimer that occludes the canonical RNA-binding surface, and instead Y14 contacts the 5′ cap structure and mRNA via a conserved tryptophan (Trp-73) to inhibit decapping by Dcp2 and recruit translation initiation factors (PMID:11296238, PMID:12730685, PMID:26887951, PMID:23115303). Beyond canonical EJC roles, Y14 undergoes SRPK1-mediated phosphorylation and liquid–liquid phase separation that concentrate Ku70/80 at DNA double-strand breaks to promote NHEJ, regulates ribosomal protein gene transcription, modulates STAT3 and NF-κB signaling independently of Magoh, and controls megakaryocyte differentiation through a p53-dependent circuit whose disruption — via compound inheritance of null and hypomorphic RBM8A alleles — causes thrombocytopenia with absent radii (TAR) syndrome (PMID:30901577, PMID:40727937, PMID:34816104, PMID:22366785). In the developing nervous system, RBM8A is required for neural progenitor proliferation and interneuron specification, and its loss causes microcephaly and altered cortical excitatory–inhibitory balance (PMID:26094033, PMID:33154347).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2001 High

    Establishing that Y14 marks exon–exon junctions on cytoplasmic mRNAs resolved where the EJC persists after export and identified Y14 as a position-specific mRNA-bound factor distinct from Aly/REF.

    Evidence Xenopus oocyte microinjection with RNase fragmentation and immunoprecipitation of cytoplasmic mRNPs

    PMID:11296238

    Open questions at the time
    • Mechanism of sequence-independent, position-specific deposition not determined
    • Whether Y14 alone is sufficient for junction marking or requires co-factors unresolved
  2. 2001 High

    Demonstrating that Drosophila Y14 interacts with Mago-nashi and is required for oskar mRNA posterior localization linked the EJC heterodimer to mRNA transport in a genetically tractable system.

    Evidence Genetic loss-of-function in Drosophila oocytes with immunohistochemistry and mRNA localization assays

    PMID:11696323

    Open questions at the time
    • Direct RNA contacts of Y14 in the localization complex not mapped
    • Whether Y14–Mago function in mRNA localization is conserved in vertebrates not tested
  3. 2002 High

    Showing that ribosome transit is required to strip Y14 from cytoplasmic mRNAs established the mechanistic link between translation and EJC removal, explaining how the complex can serve as a mark of untranslated mRNAs for NMD surveillance.

    Evidence Polysome fractionation, in vitro splicing/translation-coupled assay, and 5′UTR secondary-structure translation block

    PMID:12121612

    Open questions at the time
    • Identity of the ribosome-associated factor that directly displaces Y14 was unknown
    • Kinetics of removal per junction not measured
  4. 2003 High

    Crystal structures of Y14–Magoh from Drosophila and human revealed that Magoh occupies the canonical RNA-binding surface of Y14's RRM, explaining how Y14 binds mRNA in a sequence-independent manner and why the heterodimer is obligate for EJC function.

    Evidence X-ray crystallography at 2.5 Å and 1.85 Å (Drosophila) and at comparable resolution (human), with structure-guided mutagenesis and NMD functional assays

    PMID:12704080 PMID:12730685 PMID:12781131

    Open questions at the time
    • How the Y14–Magoh heterodimer contacts RNA through surfaces outside the RRM was unclear
    • Structural basis for EJC assembly on the spliceosome not resolved
  5. 2003 High

    Identifying that Y14 directly interacts with UPF3B and that this interaction (not UPF2–UPF3B binding) is essential for NMD established Y14 as the EJC platform for NMD factor recruitment.

    Evidence Tethered function analysis, RNAi knockdown/repletion, β-globin NS39 NMD reporter

    PMID:12718880

    Open questions at the time
    • How UPF2 is recruited when UPF2–UPF3B interaction is dispensable was unresolved
    • Stoichiometry and order of factor assembly on Y14 not determined
  6. 2004 High

    Structural characterization of the PYM–Mago–Y14 ternary complex showed how PYM caps the heterodimer interface, providing a mechanism for cytoplasmic EJC disassembly and recycling.

    Evidence X-ray crystallography (1.9 Å) of Drosophila ternary complex, pull-down, NMD tethering assay

    PMID:14968132

    Open questions at the time
    • Whether PYM-mediated disassembly is the primary pathway for ribosome-triggered EJC removal was unknown
    • Regulation of PYM access to the heterodimer not characterized
  7. 2005 High

    Demonstration that phosphorylation of Y14's RS dipeptides abolishes EJC/NMD factor interactions while arginine methylation is antagonized by phosphorylation revealed a post-translational regulatory switch governing EJC complex dynamics.

    Evidence In vitro kinase assay, phospho-mimetic/non-phosphorylatable mutants, co-immunoprecipitation, sucrose-gradient sedimentation

    PMID:16100109

    Open questions at the time
    • Identity of the specific SR kinase(s) responsible in vivo was not established
    • Physiological triggers for phosphorylation/dephosphorylation cycles unknown
  8. 2008 Medium

    Discovery that Y14 interacts with STAT3 and promotes IL-6-induced STAT3 signaling — and that Magoh antagonizes this interaction — revealed an EJC-independent signaling function for Y14.

    Evidence Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown with STAT3 phosphorylation and reporter readouts

    PMID:18503751 PMID:19254694

    Open questions at the time
    • Structural basis for STAT3–Y14 interaction not defined
    • In vivo physiological context for STAT3 regulation by Y14 not established
    • Findings from a single laboratory
  9. 2012 High

    Identifying compound inheritance of a null allele plus a regulatory SNP reducing RBM8A transcription as the genetic basis of TAR syndrome established the first Mendelian disease caused by Y14 insufficiency and linked EJC dosage to megakaryopoiesis and skeletal patterning.

    Evidence Transcriptional reporter assay, Western blot of patient platelets, genetic mapping in a large TAR cohort

    PMID:22366785

    Open questions at the time
    • Mechanistic link between Y14 reduction and radial aplasia not determined
    • Cell-type-specific thresholds for Y14 insufficiency not characterized
  10. 2012 High

    Showing that Y14 directly binds the 5′ cap and Dcp2 to inhibit mRNA decapping expanded Y14's function beyond NMD to a general mRNA stabilization role, connecting EJC occupancy with mRNA half-life control and P-body dynamics.

    Evidence In vitro decapping assay, cap-binding assay, mRNA half-life measurement, siRNA knockdown, P-body fluorescence microscopy

    PMID:23115303

    Open questions at the time
    • Whether cap binding and NMD activity are mutually exclusive on the same mRNP was unclear
    • Genome-wide identification of mRNAs protected by Y14-mediated decapping inhibition not performed
  11. 2016 High

    Pinpointing Trp-73 as the residue critical for cap-structure binding, translational enhancement, and mRNA protection — while dispensable for NMD — functionally separated Y14's translation-promoting and decay-activating activities.

    Evidence W73V site-directed mutagenesis, in vitro cap-binding assay, co-immunoprecipitation with initiation factors, in vitro/in vivo translation reporter assay

    PMID:26887951

    Open questions at the time
    • Structural model of Trp-73–cap interaction not available
    • Whether Trp-73-dependent cap binding operates within or outside the canonical EJC complex not resolved
  12. 2013 Medium

    Demonstrating that Y14 associates with RIP1/TRADD independently of Magoh/EJC to activate TNF-α–NF-κB signaling identified a second EJC-independent signaling role for Y14.

    Evidence Endogenous co-immunoprecipitation, siRNA knockdown, overexpression rescue, NF-κB reporter assay

    PMID:23817415

    Open questions at the time
    • Mechanism by which Y14 enhances RIP1–TRADD binding not defined
    • Single laboratory finding
    • In vivo validation in immune cells lacking
  13. 2015 High

    Bidirectional manipulation in embryonic cortical progenitors showed RBM8A promotes neural progenitor proliferation and suppresses premature neuronal differentiation, establishing a role for EJC dosage in cortical development.

    Evidence In utero electroporation (overexpression/knockdown), BrdU/EdU incorporation, RNA-seq

    PMID:26094033

    Open questions at the time
    • Direct mRNA targets mediating the NPC phenotype not individually validated
    • Whether NMD or alternative splicing activity of Y14 is the primary driver not separated
  14. 2017 Medium

    Identification of Y14-dependent suppression of aberrant p53β exon inclusion established a specific alternative splicing target through which EJC dosage modulates the p53 pathway and genotoxic stress sensitivity.

    Evidence siRNA knockdown, RT-PCR splice isoform analysis, Western blot, cell viability assay

    PMID:28361991

    Open questions at the time
    • Whether p53β splicing change is direct (Y14 binding at the regulated junction) not confirmed
    • Single laboratory finding
  15. 2019 High

    Discovering that Y14 interacts with Ku and DDR factors in an ATM-dependent manner, accumulates on damaged chromatin, and promotes NHEJ established a direct DNA-repair function for Y14 beyond mRNA metabolism.

    Evidence IP-mass spectrometry, chromatin fractionation, γH2AX foci assay, DNA end-joining assay, R-loop detection

    PMID:30901577

    Open questions at the time
    • Whether Y14's DNA repair role requires its RNA-binding activity or operates through protein–protein interactions alone was unknown
    • Structural basis for Y14–Ku interaction not determined
  16. 2020 High

    Conditional knockout studies in neural stem cells demonstrated that Rbm8a is essential for brain size, interneuron specification, and cortical excitatory–inhibitory balance, providing a developmental mechanism for neurodevelopmental consequences of RBM8A haploinsufficiency.

    Evidence Conditional KO (NES-Cre, NKX2.1-Cre), immunohistochemistry, electrophysiology, RNA-seq

    PMID:33154347

    Open questions at the time
    • Specific mRNA targets responsible for interneuron versus excitatory neuron phenotypes not individually identified
    • Whether behavioral phenotypes accompany the circuit defects not tested
  17. 2021 High

    Megakaryocyte-specific Rbm8a knockout recapitulated TAR thrombocytopenia and established that Y14 deficiency activates p53/p21 in megakaryocytes, with p53 deletion partially rescuing platelet counts — defining the Y14–p53 circuit as the pathogenic mechanism in TAR syndrome.

    Evidence Megakaryocyte-specific conditional KO, Trp53 double-KO genetic epistasis, p53 inhibitor rescue, platelet count/activation assays

    PMID:34816104

    Open questions at the time
    • Which specific p53-activating mRNA(s) are deregulated in Y14-deficient megakaryocytes is unknown
    • Whether p53 inhibition can fully rescue radial aplasia not addressed
  18. 2022 Medium

    Acute RBM8A depletion combined with nascent transcription analysis revealed that RBM8A globally regulates ribosomal protein gene transcription, extending its function to a transcriptional role beyond post-transcriptional mRNA metabolism.

    Evidence Auxin degron acute depletion, SLAM-seq/GRO-seq, CRISPR-KO screen

    PMID:36187487

    Open questions at the time
    • Whether RBM8A acts at ribosomal protein gene promoters directly or via an indirect mRNA/splicing-dependent mechanism is unresolved
    • Single laboratory finding
  19. 2023 Medium

    Reconstitution of Y14 liquid–liquid phase separation in vitro, driven by its low-complexity charged termini and suppressed by RS-repeat phosphomimicry, provided a biophysical mechanism for Y14 condensate formation and linked LLPS capacity to DNA repair activity.

    Evidence Recombinant protein LLPS assay, domain deletion/phosphomimetic mutants, in vitro RNA coacervation, DSB repair functional assay

    PMID:37001915

    Open questions at the time
    • In vivo evidence for Y14 phase-separated condensates at DNA damage sites was indirect
    • Contribution of LLPS versus stable protein–protein interactions to Ku recruitment not separated
  20. 2025 Medium

    Identification of SRPK1 as the kinase phosphorylating Y14 for DNA-damage site recruitment, and demonstration that Mg²⁺-dependent LLPS of phosphorylated Y14 concentrates Ku70/80 at breaks, unified the phosphorylation, phase-separation, and NHEJ functions into a coherent damage-response pathway.

    Evidence Live-cell imaging (HaloTag-Y14 at laser damage), in vitro LLPS with phosphomimetic mutants, Ku partitioning assay, SRPK1 inhibitor, divalent cation chelation

    PMID:40727937

    Open questions at the time
    • Whether SRPK1-mediated phosphorylation of Y14 at damage sites is coordinated with ATM-dependent interactions identified earlier is not resolved
    • In vivo reconstitution of Mg²⁺-dependent condensate not performed
    • Single laboratory finding
  21. 2025 High

    Zebrafish rbm8a mutants revealed that EJC-dependent splicing of Wnt/PCP pathway transcripts (wnt5b, vangl2, fzd7a) is required for convergent extension and hematopoietic specification, providing a developmental signaling pathway regulated by RBM8A-mediated intron retention control.

    Evidence Zebrafish genetic mutant, rbm8a × vangl2 double-mutant epistasis, RNA-seq for intron retention, live imaging

    PMID:40907933

    Open questions at the time
    • Whether Wnt/PCP splicing regulation by RBM8A is conserved in mammals not tested
    • Direct binding of Y14 to the retained introns not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RBM8A's multiple functions — EJC-dependent NMD, translational enhancement, decapping inhibition, transcriptional regulation, NHEJ repair via LLPS, and signaling modulation — are partitioned across distinct RBM8A pools within the cell, and which functions are most dosage-sensitive in TAR syndrome pathology beyond megakaryopoiesis, remain unresolved.
  • No structural model of Y14 bound to the 5′ cap or to Ku70/80
  • Genome-wide mapping of Y14-dependent NHEJ sites not available
  • Relative contributions of NMD, splicing, and transcriptional roles to TAR pathogenesis in skeletal tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005654 nucleoplasm 3 GO:0005829 cytosol 3 GO:0005694 chromosome 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-8953854 Metabolism of RNA 6 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-73894 DNA Repair 3 R-HSA-109582 Hemostasis 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-74160 Gene expression (Transcription) 1
Partners
DCP2EIF4A3MAGOHNXF1PYM1STAT3UPF3BXRCC6
Complex memberships
Exon Junction Complex (EJC)PRMT5 methylosomeY14–Magoh heterodimer

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Y14 (RBM8A) binds stably to sequences immediately upstream of exon-exon junctions on spliced mRNAs, as shown by microinjection of pre-mRNAs into Xenopus oocyte nuclei followed by immunoprecipitation of RNase-fragmented cytoplasmic mRNAs; this position-specific binding is unique to Y14 among EJC components (Aly/REF is not detected on cytoplasmic mRNAs). Xenopus oocyte microinjection, cytoplasmic immunoprecipitation of RNase-fragmented mRNAs The EMBO journal High 11296238
2001 Drosophila Y14 interacts with Mago-nashi in vivo, colocalizes with oskar mRNA at the posterior pole of the oocyte, and is required for oskar mRNA posterior localization (not for cytoskeleton integrity), establishing Y14 as part of the oskar mRNA localization complex. Immunohistochemistry, genetic loss-of-function (y14 mutant oocytes), mRNA localization assay Current biology : CB High 11696323
2002 Y14 remains associated with mRNAs in the cytoplasm until they are translated; translation (ribosome transit) is required to remove Y14 from mRNAs, as shown by polysome profiling, in vitro splicing/translation-coupled reporter assays, and prevention of removal by strong 5'UTR secondary structures that block translation in vivo. Polysome fractionation, in vitro splicing/translation-coupled reporter assay, 5'UTR secondary-structure block in vivo Current biology : CB High 12121612
2003 Y14 directly interacts with hUpf3b via a conserved domain of hUpf3b; this Y14/hUpf3b interaction is essential for NMD (tethered function and RNAi knockdown/repletion assays), while hUpf2-hUpf3b interaction is dispensable. hUpf2 is nonetheless required for NMD activated by tethered Y14. Tethered function analysis, RNAi knockdown and repletion, co-immunoprecipitation, beta-globin NS39 NMD reporter assay Molecular cell High 12718880
2003 Crystal structure of the Drosophila Y14–Mago complex at 2.5 Å reveals that the canonical RNA-binding surface (RNP1/RNP2 motifs) of the Y14 RBD is used for protein–protein interaction with Mago rather than RNA binding; structure-guided mutagenesis shows Mago is required for NMD and that Y14–Mago association is essential for function. X-ray crystallography (2.5 Å), structure-guided mutagenesis, NMD functional assay Nature structural biology High 12730685
2003 High-resolution crystal structure (1.85 Å) of Drosophila Mago–Y14 complex confirms that the canonical RNA-binding surface of the Y14 RRM is engaged in extensive protein–protein interactions with Mago, and Magoh binds with high affinity to Y14's RBD, masking its RNA-binding surface. X-ray crystallography (1.85 Å), biochemical binding assays Genes & development High 12704080
2003 Human Y14 and Magoh form a stable heterodimer in which Magoh binds with high affinity to the RBD of Y14 and completely masks its RNA-binding surface; the complex has an unusual flat beta-sheet structure (Magoh), providing insight into how the EJC assembles at splice junctions independent of RNA sequence. X-ray crystallography, biochemical affinity assays Current biology : CB High 12781131
2004 PYM interacts directly with the Mago–Y14 heterodimer via its N-terminal domain, capping the heterodimerization interface at conserved residues; crystal structure of the ternary Drosophila Mago–Y14–PYM complex at 1.9 Å shows PYM binds Mago and Y14 simultaneously. PYM is a cytoplasmic protein excluded from the nucleus by Crm1 and is active in NMD tethering assays. X-ray crystallography (1.9 Å), pull-down, NMD tethering assay, nuclear export inhibition EMBO reports High 14968132
2005 Y14 is phosphorylated at its RS dipeptide repeats, likely by SR-protein-specific kinases; phosphorylation abolishes Y14 interactions with EJC components and downstream NMD factors. A non-phosphorylatable mutant retains NMD activity but sequesters EJC/NMD factors on ribosome-associated mRNPs. Y14 is also methylated at arginine residues in its C-terminal domain, and methylation is antagonized by RS phosphorylation. In vitro kinase assay, phospho-mimetic/non-phosphorylatable mutants, co-immunoprecipitation, sucrose-gradient sedimentation The Journal of biological chemistry High 16100109
2006 Y14 and NXF1 (mRNA export factor) form complexes in vivo, visualized by BiFC within and around nuclear speckles (SC35 domains); the complexes depend on active transcription and full-length NXF1. FRAP/FLIP show ~half of accumulated BiFC complexes are immobile in vivo and are depleted by ATP in permeabilized cells, indicating ATP-dependent retention of a Y14-containing mRNA-export complex in speckles. Bimolecular fluorescence complementation (BiFC), co-immunoprecipitation, FRAP, FLIP, permeabilized-cell ATP depletion The Journal of cell biology High 16431928
2008 Y14 interacts with STAT3 through the C-terminal region of STAT3, as shown by yeast two-hybrid screening and confirmed in vivo; siRNA-mediated reduction of Y14 decreases IL-6-induced STAT3 tyrosine phosphorylation, nuclear accumulation, DNA-binding activity, and IL-6/STAT3-dependent gene expression. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, STAT3 phosphorylation/nuclear translocation assays, reporter gene assay Biochemical and biophysical research communications Medium 18503751
2009 MAGOH, the Y14 binding partner in the EJC, inhibits the STAT3–Y14 complex formation; siRNA knockdown of MAGOH enhances IL-6-induced STAT3-dependent gene expression, indicating that MAGOH negatively regulates the Y14–STAT3 interaction. Co-immunoprecipitation (endogenous), siRNA knockdown, IL-6-induced gene expression assay Biochemical and biophysical research communications Medium 19254694
2011 Y14/Magoh heterodimer (but not other EJC factors) interacts with the cytoplasmic PRMT5-containing methylosome; Y14 promotes PRMT5-mediated methylation of Sm proteins of the snRNP core, and Y14 overexpression induces formation of a large, active, snRNP-associated methylosome complex. Y14 knockdown reduces Sm protein methylation. Co-immunoprecipitation, methylation assay, siRNA knockdown, sucrose-gradient sedimentation The Journal of biological chemistry Medium 21209085
2011 A Y14 nuclear localization signal (YNS) in the N-terminal region also confers nuclear export; a 12-amino-acid peptide near Y14's C-terminus is required for association with spliced mRNAs and for Magoh binding. Y14 mutants deficient in Magoh binding still localize to the nucleus, indicating a Magoh-independent nuclear import pathway. Domain deletion and point mutant analysis, nuclear/cytoplasmic fractionation, immunofluorescence, co-immunoprecipitation Scientific reports Medium 22355610
2012 Y14 (RBM8A) insufficiency, caused by compound inheritance of a null allele and a regulatory SNP reducing RBM8A transcription, underlies TAR syndrome; the regulatory SNPs result in diminished RBM8A transcription in vitro and reduced Y14 protein in platelets from TAR individuals. Transcriptional reporter assay (in vitro), Western blot of patient platelets, genetic mapping Nature genetics High 22366785
2012 Y14/Magoh specifically associates with mRNA-decapping factors (Dcp2, exoribonucleases) but not with eIF4AIII/MLN51; Y14 directly interacts with Dcp2 and the 5' cap structure via different but overlapping domains and inhibits Dcp2 decapping activity in vitro. Y14 overexpression prolongs reporter mRNA half-life; Y14 depletion disrupts P-body formation, whereas phosphomimetic Y14 overexpression increases P-body number. In vitro decapping assay, co-immunoprecipitation, cap-binding assay, mRNA half-life measurement, siRNA knockdown, fluorescence microscopy of P-bodies Molecular biology of the cell High 23115303
2013 Depletion of RBM8A in A549 cells causes accumulation of mitotic cells, G2/M arrest, multipolar/monopolar centrosome defects, activation of caspases 3/7, and apoptosis. Silencing of either RBM8A or Magoh causes mutual downregulation of the other protein. siRNA knockdown, flow cytometry, centrosome immunostaining, caspase activity assay Experimental biology and medicine Medium 23970407
2013 RBM8A-MAGOH complex localizes to centrosomes (in addition to nucleoplasm) in human A549 cells, as shown by immunostaining of endogenous and tagged proteins, proximity ligation assay confirming complex formation at centrosomes, and co-localization with PLK1. This centrosomal localization underlies M-phase progression defects upon RBM8A depletion. Immunofluorescence, proximity ligation in situ assay, eYFP/Flag tagged protein expression, co-localization with PLK1 Histochemistry and cell biology Medium 23949737
2013 Y14 positively regulates TNF-α–induced NF-κB activation by directly associating (endogenously) with RIP1 and TRADD; Y14 enhances RIP1–TRADD binding and acts downstream of TRADD and upstream of RIP1 in the TNF-α–NF-κB pathway. This function is independent of MAGOH/EJC. Co-immunoprecipitation (endogenous), siRNA knockdown, overexpression rescue, NF-κB reporter assay, IκBα phosphorylation/degradation assay Journal of immunology Medium 23817415
2015 RBM8a overexpression in embryonic cortical neural progenitor cells (NPCs) stimulates proliferation and suppresses neuronal differentiation/cell cycle exit, while knockdown reduces NPC proliferation and promotes premature neuronal differentiation. RBM8a regulates alternative splicing and NMD targets implicated in ASD. In utero electroporation (overexpression/knockdown), BrdU/EdU incorporation, immunostaining for differentiation markers, genome-wide RNA-seq Neural development High 26094033
2016 An evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for cap-structure binding; the W73V mutant binds mRNAs weakly, cannot interact with translation initiation factors, fails to protect mRNAs from degradation, and suppresses reporter mRNA translation in vitro and in vivo, while retaining partial NMD activity and interaction with NMD/degradation factors. Site-directed mutagenesis, in vitro cap-binding assay, co-immunoprecipitation, in vitro/in vivo translation reporter assay, mRNA stability assay The Journal of biological chemistry High 26887951
2017 Y14, as part of the EJC, suppresses aberrant exon inclusion during p53 pre-mRNA splicing, thereby preventing expression of the p53β isoform. Y14 depletion induces p53β expression and elevates total p53 protein levels while reducing p21 protein, increasing cell sensitivity to genotoxic agents. siRNA knockdown, RT-PCR splice isoform analysis, Western blot, cell viability/genotoxicity assay Scientific reports Medium 28361991
2018 The C-terminal RS repeat-containing region of Y14 controls its subcellular localization: deletion or dephosphorylation-mimetic mutations of this region shift Y14 from nucleoplasm, and the C-terminal sequence itself confers nucleolar localization potential. MAGOH binding to Y14 further modulates this localization. Deletion/phosphomimetic/non-phosphorylatable mutants, immunofluorescence, transfection Scientific reports Medium 29330450
2019 Y14 depletion or Rbm8a haplodeficiency causes accumulation of DNA damage and R-loops. Y14 interacts (in an ATM-dependent manner) with Ku and several DDR factors (identified by IP-mass spectrometry). Y14 co-fractionates with Ku in chromatin-enriched fractions, accumulates on chromatin upon DNA damage, and its knockdown delays DDR factor recruitment, γH2AX foci formation, and Ku removal from chromatin, compromising DNA end-joining efficiency. IP-mass spectrometry, co-immunoprecipitation, chromatin fractionation, γH2AX foci assay, DNA end-joining assay, R-loop detection, siRNA knockdown iScience High 30901577
2019 Stability of Y14 and Magoh proteins depends on their heterodimer formation and nuclear localization: leucine-to-arginine mutations (Y14 L118R, Magoh L136R) that abolish heterodimerization accelerate protein degradation (cycloheximide chase), with nuclear localization providing additional stability to Y14 L118R. Point mutagenesis, cycloheximide chase assay, co-immunoprecipitation, immunofluorescence Biochemical and biophysical research communications Medium 30826064
2020 In zebrafish, homozygous rbm8a mutations cause muscle disorganization, neural cell death, and motor neuron outgrowth defects. EJC-dependent NMD via rbm8a regulates mRNAs with 3'UTR introns <50 nts downstream of the stop codon (proximal 3'UI), including foxo3b; loss of foxo3b function in rbm8a mutants significantly rescues motor axon growth defects, placing rbm8a upstream of foxo3b mRNA regulation. Genetic loss-of-function (zebrafish mutant), RNA-seq, epistasis (double mutant rescue), Western blot, immunostaining PLoS genetics High 32502192
2020 Conditional knockout of Rbm8a in neural stem cells causes microcephaly, postnatal lethality, and altered excitatory neuron distribution; Rbm8a haploinsufficiency decreases proliferation in ganglionic eminences, reduces parvalbumin+ and NPY+ interneurons, and decreases cortical GABA frequency. Transcriptomic analysis identifies DEGs enriched in telencephalon development and mitosis. Conditional KO (NES-Cre, NKX2.1-Cre), immunohistochemistry, electrophysiology (mEPSC/mIPSC), RNA-seq Translational psychiatry High 33154347
2021 Megakaryocyte-specific Rbm8a knockout mice exhibit thrombocytopenia, internal hemorrhage, splenomegaly, and accumulation of low-ploidy immature megakaryocytes; Y14/RBM8A deficiency induces p53 and p21 in megakaryocytes. A p53 inhibitor restores ex vivo differentiation and Trp53 KO partially rescues platelet counts in Rbm8aKOMK mice, establishing a Y14–p53 circuit in platelet production. Megakaryocyte-specific conditional KO, platelet count/activation assays, p53 inhibitor treatment, Trp53 double-KO epistasis, Western blot iScience High 34816104
2022 RBM8A is a global regulator of ribosomal protein gene transcription: acute depletion of RBM8A (auxin degron system) combined with genome-wide nascent transcription analysis (SLAM-seq/GRO-seq) shows RBM8A controls transcript levels of ribosomal protein mRNAs, including intronless reporter genes. Auxin degron acute depletion, CRISPR-KO screen, FACS-sorted reporter cell line, genome-wide nascent transcription analysis Frontiers in cell and developmental biology Medium 36187487
2023 Recombinant Y14 undergoes liquid-liquid phase separation (LLPS) in vitro via multivalent electrostatic interactions involving its low-complexity N- and C-terminal charged regions; phospho-mimicry of C-terminal RS dipeptides suppresses LLPS. RNA co-phase-separates into Y14 droplets in a concentration-dependent manner. LLPS capacity correlates with Y14's activity in DNA double-strand break repair. Recombinant protein LLPS assay, domain deletion/phosphomimetic mutants, in vitro RNA coacervation, DSB repair functional assay RNA (New York, N.Y.) Medium 37001915
2024 hsa_circ_0081343 sequesters Rbm8a in the cytoplasm; knockdown of hsa_circ_0081343 facilitates Rbm8a nuclear translocation via Importin-13 (Ipo13), which recognizes Rbm8a through a functional NLS. Nuclear Rbm8a activates trophoblast autophagy. RNA pulldown, mass spectrometry, RNA immunoprecipitation, co-immunoprecipitation, immunofluorescence, Western blot Placenta Medium 39413593
2025 SRPK1-mediated phosphorylation of Y14 is required for its localization to laser-induced DNA damage sites and for DSB repair; phosphorylated Y14 undergoes Mg2+-promoted LLPS in vitro, and Ku70/80 partitions into phosphorylated Y14 condensates. Chelation of divalent cations abolishes Y14 localization and NHEJ factor recruitment at damage sites. Inhibition of Y14 phosphorylation impairs Ku70/80 recruitment and sensitizes cancer cells to DNA damage. Live-cell imaging (HaloTag-Y14, laser-induced damage), in vitro LLPS with phosphomimetic mutants, Ku70/80 partitioning assay, SRPK1 inhibitor, divalent cation chelation, cell viability/sensitivity assay iScience Medium 40727937
2025 RBM8A recruits the RNA helicase eIF4A3 to stabilize EGFR mRNA, shielding it from exonucleolytic degradation; this sustains nuclear EGFR–DNA-PKcs complex formation to drive NHEJ-mediated DNA repair and suppress oxaliplatin-induced apoptosis in gastric cancer. RIP-seq, RNA immunoprecipitation, mRNA stability assay, Co-immunoprecipitation, siRNA screen, xenograft model Oncogene Medium 41354714
2025 RBM8A interacts with UPF3B to promote degradation of BBC3 (PUMA) mRNA in gastric cancer cells; direct RBM8A–BBC3 mRNA interaction was confirmed by RIP, FISH-IF, and RNA pulldown. Actinomycin D assays showed RBM8A promotes BBC3 mRNA degradation, suppressing apoptosis. Co-immunoprecipitation, RNA immunoprecipitation, RNA pulldown, FISH-immunofluorescence, mRNA stability (actinomycin D) assay, RIP-seq International journal of molecular medicine Medium 40613240
2025 PYM1 mediates translation-independent EJC disassembly from non-canonical positions (away from canonical EJC binding sites, including intronless transcripts); PYM1-interaction-deficient EJCs accumulate on transcripts with fewer and longer exons. PYM1 depletion modestly inhibits NMD and stabilizes mRNAs localizing to ER-associated TIS granules. Flavivirus capsid protein hijacks PYM1 to globally alter EJC occupancy and reshape host mRNA regulation. CLIP-seq (EJC occupancy), NMD reporter assay, mRNA stability assay, virus infection, PYM1 depletion (siRNA/auxin degron), co-immunoprecipitation bioRxivpreprint Medium bio_10.1101_2025.03.13.643037
2025 In zebrafish, rbm8a deficiency causes hematopoietic defects via attenuated non-canonical Wnt/Planar Cell Polarity (PCP) signaling: rbm8a mutants accumulate mRNAs with retained introns from Wnt/PCP pathway components (wnt5b, wnt11f2, fzd7a, vangl2), show convergent extension defects, impaired lateral plate mesoderm architecture, and reduced expression of hematopoietic/endothelial genes runx1 and gfi1aa. Genetic interaction between rbm8a and vangl2 was established. Zebrafish genetic mutant, genetic epistasis (rbm8a × vangl2 double mutant), RNA-seq (intron retention), live imaging, immunostaining Developmental biology High 40907933

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Compound inheritance of a low-frequency regulatory SNP and a rare null mutation in exon-junction complex subunit RBM8A causes TAR syndrome. Nature genetics 325 22366785
2003 Y14 and hUpf3b form an NMD-activating complex. Molecular cell 251 12718880
2002 Translation is required to remove Y14 from mRNAs in the cytoplasm. Current biology : CB 185 12121612
2001 Drosophila Y14 shuttles to the posterior of the oocyte and is required for oskar mRNA transport. Current biology : CB 178 11696323
2001 The Y14 protein communicates to the cytoplasm the position of exon-exon junctions. The EMBO journal 163 11296238
2003 A novel mode of RBD-protein recognition in the Y14-Mago complex. Nature structural biology 146 12730685
2003 Structure of the Y14-Magoh core of the exon junction complex. Current biology : CB 102 12781131
2004 Molecular insights into the interaction of PYM with the Mago-Y14 core of the exon junction complex. EMBO reports 82 14968132
2003 Crystal structure of the Drosophila Mago nashi-Y14 complex. Genes & development 79 12704080
2006 In vivo BiFC analysis of Y14 and NXF1 mRNA export complexes: preferential localization within and around SC35 domains. The Journal of cell biology 59 16431928
2019 Identification of molecular correlations of RBM8A with autophagy in Alzheimer's disease. Aging 54 31816601
2019 Expression and gene regulation network of RBM8A in hepatocellular carcinoma based on data mining. Aging 48 30670676
2013 Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells. Experimental biology and medicine (Maywood, N.J.) 48 23970407
2001 The genes encoding the type II gonadotropin-releasing hormone receptor and the ribonucleoprotein RBM8A in humans overlap in two genomic loci. Genomics 47 11707068
2015 A critical role of RBM8a in proliferation and differentiation of embryonic neural progenitors. Neural development 44 26094033
2012 The RNA-binding protein Y14 inhibits mRNA decapping and modulates processing body formation. Molecular biology of the cell 44 23115303
2000 Identification and structural analysis of human RBM8A and RBM8B: two highly conserved RNA-binding motif proteins that interact with OVCA1, a candidate tumor suppressor. Genomics 44 11013075
2005 Phosphorylation of Y14 modulates its interaction with proteins involved in mRNA metabolism and influences its methylation. The Journal of biological chemistry 40 16100109
2013 An EJC factor RBM8a regulates anxiety behaviors. Current molecular medicine 39 23638902
2007 Mago Nashi and Tsunagi/Y14, respectively, regulate Drosophila germline stem cell differentiation and oocyte specification. Developmental biology 28 17628520
2011 The exon junction complex component Y14 modulates the activity of the methylosome in biogenesis of spliceosomal small nuclear ribonucleoproteins. The Journal of biological chemistry 27 21209085
2006 Biochemical and cellular characterization of the plant ortholog of PYM, a protein that interacts with the exon junction complex core proteins Mago and Y14. Planta 26 16953428
2013 RNA-binding protein RBM8A (Y14) and MAGOH localize to centrosome in human A549 cells. Histochemistry and cell biology 25 23949737
2015 Function and pathological implications of exon junction complex factor Y14. Biomolecules 23 25866920
2014 Slow co-evolution of the MAGO and Y14 protein families is required for the maintenance of their obligate heterodimerization mode. PloS one 23 24416299
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
2008 An RNA biding protein, Y14 interacts with and modulates STAT3 activation. Biochemical and biophysical research communications 22 18503751
2020 TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A. Human mutation 21 32227665
2022 CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA. Cell death discovery 20 35568705
2017 Y14 governs p53 expression and modulates DNA damage sensitivity. Scientific reports 20 28361991
2020 Full function of exon junction complex factor, Rbm8a, is critical for interneuron development. Translational psychiatry 19 33154347
2019 The RNA Processing Factor Y14 Participates in DNA Damage Response and Repair. iScience 19 30901577
2021 Mechanism and Molecular Network of RBM8A-Mediated Regulation of Oxaliplatin Resistance in Hepatocellular Carcinoma. Frontiers in oncology 18 33552961
2021 RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway. Frontiers in oncology 17 34804926
2011 Specific Y14 domains mediate its nucleo-cytoplasmic shuttling and association with spliced mRNA. Scientific reports 17 22355610
2010 Mago Nashi, Tsunagi/Y14, and Ranshi form a complex that influences oocyte differentiation in Drosophila melanogaster. Developmental biology 16 20045686
2013 Y14 positively regulates TNF-α-induced NF-κB transcriptional activity via interacting RIP1 and TRADD beyond an exon junction complex protein. Journal of immunology (Baltimore, Md. : 1950) 15 23817415
2013 Prenatal detection of TAR syndrome in a fetus with compound inheritance of an RBM8A SNP and a 334‑kb deletion: a case report. Molecular medicine reports 15 24220582
2015 Thrombocytopenia-absent radius (TAR) syndrome due to compound inheritance for a 1q21.1 microdeletion and a low-frequency noncoding RBM8A SNP: a new familial case. Molecular cytogenetics 14 26550033
2018 C-terminal short arginine/serine repeat sequence-dependent regulation of Y14 (RBM8A) localization. Scientific reports 13 29330450
2016 A Point Mutation in the Exon Junction Complex Factor Y14 Disrupts Its Function in mRNA Cap Binding and Translation Enhancement. The Journal of biological chemistry 13 26887951
1968 Purification of beta-glucosidase from Saccharomyces lactis strains Y-14 and Y-1057A. Journal of bacteriology 12 5685996
2021 The Y14-p53 regulatory circuit in megakaryocyte differentiation and thrombocytopenia. iScience 10 34816104
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2022 The glycolytic enzyme ALDOA and the exon junction complex protein RBM8A are regulators of ribosomal biogenesis. Frontiers in cell and developmental biology 8 36187487
2022 Exon-dependent transcriptional adaptation by exon-junction complex proteins Y14/RNP-4 and MAGOH/MAG-1 in Caenorhabditis elegans. PLoS genetics 8 36315586
2019 Exon junction complex components Y14 and Mago still play a role in budding yeast. Scientific reports 8 30696855
2019 Caveolin-1 Y14 phosphorylation suppresses tumor growth while promoting invasion. Oncotarget 8 31803361
2024 Rbm8a regulates neurogenesis and reduces Alzheimer's disease-associated pathology in the dentate gyrus of 5×FAD mice. Neural regeneration research 6 37843222
2022 Thrombocytopenia-Absent Radius Syndrome: Descriptions of Three New Cases and a Novel Splicing Variant in RBM8A That Expands the Spectrum of Null Alleles. International journal of molecular sciences 6 36077017
2019 The stability of Magoh and Y14 depends on their heterodimer formation and nuclear localization. Biochemical and biophysical research communications 5 30826064
2024 Circular RNA hsa_circ_0081343 modulates trophoblast autophagy through Rbm8a nuclear translocation. Placenta 4 39413593
2023 Co-phase separation of Y14 and RNA in vitro and its implication for DNA repair. RNA (New York, N.Y.) 4 37001915
2024 Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling. bioRxiv : the preprint server for biology 3 37090609
2024 RBM8A, a new target of TEAD4, promotes breast cancer progression by regulating IGF1R and IRS-2. Journal of translational medicine 3 39232805
2021 A Comprehensive Pan-Cancer Analysis of RBM8A Based on Data Mining. Journal of oncology 3 34326876
2016 Identification and characterization of MAGO and Y14 genes in Hevea brasiliensis. Genetics and molecular biology 3 27007901
2013 Schistosoma japonicum: Tsunagi/Y14 protein plays a critical role in the development of the reproductive organs and eggs. Experimental parasitology 3 23973739
2022 RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway. The breast journal 2 36105365
2025 hsa_circ_0081343 interacts with Rbm8a to inhibit NLRP3-mediated pyroptosis via the PI3K/AKT/HIF-1α pathways. Placenta 1 40267529
2025 Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling. Developmental biology 1 40907933
2025 RBM8A confers oxaliplatin resistance in gastric cancer by maintaining EGFR mRNA stability. Oncogene 1 41354714
2024 The Exon Junction Complex Factor RBM8A in Glial Fibrillary Acid Protein-Expressing Astrocytes Modulates Locomotion Behaviors. Cells 1 38534343
2023 Transcriptomic Analyses of Brains of RBM8A Conditional Knockout Mice at Different Developmental Stages Reveal Conserved Signaling Pathways Contributing to Neurodevelopmental Diseases. International journal of molecular sciences 1 36902031
2017 The exon junction complex factor Y14 is dynamic in the nucleus of the beetle Tribolium castaneum during late oogenesis. Molecular cytogenetics 1 29151891
2026 Estimation of Double-Serine Phosphorylation's Effects on the Intrinsically Disordered Region Structure in Y14 (RBM8A) Protein via Molecular Dynamics Simulation. Cells 0 41972736
2025 RBM8A promotes gastric cancer progression by binding with UPF3B to induce BBC3 mRNA degradation. International journal of molecular medicine 0 40613240
2025 Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair. iScience 0 40727937
2022 Erratum: The glycolytic enzyme ALDOA and the exon junction complex protein RBM8A are regulators of ribosomal biogenesis. Frontiers in cell and developmental biology 0 36393862