Affinage

RBM8A

RNA-binding protein 8A · UniProt Q9Y5S9

Length
174 aa
Mass
19.9 kDa
Annotated
2026-06-10
72 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM8A (Y14) is a core subunit of the exon junction complex (EJC) that controls the fate of spliced mRNAs from nuclear processing through cytoplasmic translation, and additionally serves EJC-independent roles in genome maintenance and signaling (PMID:11296238, PMID:12121612). It binds spliced mRNA in a position-specific but RNA-sequence-independent manner by heterodimerizing with MAGOH, whose flat beta-sheet engages and masks the RNA-binding surface of the Y14 RRM, explaining why deposition is dictated by exon-exon junction position rather than sequence (PMID:11296238, PMID:12781131, PMID:12704080). Y14 persists on mRNAs through nuclear export and is removed in the cytoplasm by translating ribosomes; PYM caps the Mago-Y14 interface to drive disassembly (PMID:12121612, PMID:14968132). From this platform Y14 coordinates downstream RNA fates: it activates nonsense-mediated mRNA decay through a direct interaction with UPF3B that is essential for NMD (PMID:12718880, PMID:12730685), enhances translation and protects mRNA via a conserved Trp-73 cap-binding residue (PMID:26887951), and inhibits Dcp2-mediated decapping to stabilize transcripts and modulate P-body formation (PMID:23115303). Beyond canonical EJC functions, Y14 promotes PRMT5-mediated methylation of Sm proteins during snRNP biogenesis (PMID:21209085), regulates p53 pre-mRNA splicing and protein levels (PMID:28361991), and participates in DNA double-strand break repair, where SRPK1-driven phosphorylation promotes Mg2+-dependent liquid-liquid phase separation that recruits Ku70/80 and NHEJ factors to damage sites (PMID:30901577, PMID:37001915, PMID:40727937). Phosphorylation of its C-terminal RS dipeptides governs EJC/NMD-factor association, subcellular localization, and phase-separation capacity (PMID:16100109, PMID:29330450, PMID:37001915). EJC-independent activities include positive regulation of STAT3 and TNF-α-induced NF-κB signaling (PMID:18503751, PMID:23817415). Developmentally, Y14 maintains neural progenitor proliferation and influences interneuron production and cortical GABAergic signaling (PMID:26094033, PMID:33154347), and operates in a Y14-p53 circuit required for megakaryocyte differentiation and platelet production (PMID:34816104). RBM8A insufficiency, through compound inheritance of a null allele with hypomorphic regulatory SNPs, causes thrombocytopenia-absent radius (TAR) syndrome (PMID:22366785).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 2001 High

    Established that Y14 is deposited on spliced mRNA at a fixed position upstream of exon junctions and uniquely persists into the cytoplasm, defining it as a mark of splicing history rather than a sequence-specific binder.

    Evidence Xenopus oocyte microinjection with RNase mapping and cytoplasmic fractionation; in vivo Drosophila genetics showing Mago-nashi interaction and oskar mRNA localization

    PMID:11296238 PMID:11696323

    Open questions at the time
    • Did not resolve how position-specific deposition is achieved mechanistically
    • Cytoplasmic function of persistent Y14 not yet defined
  2. 2002 High

    Answered how the cytoplasmic EJC mark is erased, showing translation displaces Y14 and links its removal to ribosome transit.

    Evidence Polysome profiling, coupled in vitro splicing/translation, and in vivo 5' UTR structural block

    PMID:12121612

    Open questions at the time
    • Did not identify the factor that physically strips Y14 from translated mRNA
  3. 2003 High

    Defined the molecular basis of EJC assembly and its coupling to NMD: MAGOH binds the Y14 RRM RNA surface, and the Y14-UPF3b axis is the essential NMD-activating interaction.

    Evidence Multiple independent crystal structures of Y14-Mago(h) and tethered-function/RNAi NMD assays with UPF3b

    PMID:12704080 PMID:12718880 PMID:12730685 PMID:12781131

    Open questions at the time
    • Did not explain how the EJC signals decay across long distances on mRNA
  4. 2004 High

    Identified PYM as the disassembly factor that caps the Mago-Y14 interface, providing a mechanism for cytoplasmic EJC recycling.

    Evidence Crystal structure of the PYM-Mago-Y14 ternary complex with binding and NMD tethering assays

    PMID:14968132

    Open questions at the time
    • Did not separate translation-dependent from translation-independent disassembly roles of PYM
  5. 2005 High

    Showed that RS-dipeptide phosphorylation and arginine methylation toggle Y14's ability to engage EJC and NMD factors, establishing post-translational control of complex assembly.

    Evidence Phosphorylation/methylation mapping, SR-kinase inhibition, and non-phosphorylatable mutants with polysome fractionation

    PMID:16100109

    Open questions at the time
    • Specific kinase identity not pinned down at this stage
    • Physiological triggers of PTM switching unknown
  6. 2006 Medium

    Connected Y14 to nuclear mRNA export by demonstrating an NXF1 complex retained in an ATP-dependent manner near nuclear speckles.

    Evidence BiFC, RNA co-IP, and FRAP/FLIP with ATP depletion in permeabilized cells

    PMID:16431928

    Open questions at the time
    • Single-lab; molecular basis of ATP-dependent retention not defined
    • Functional consequence of speckle retention for export not directly tested
  7. 2008 Medium

    Extended Y14 beyond RNA metabolism, identifying it as a STAT3 cofactor required for IL-6-induced STAT3 activation.

    Evidence Yeast two-hybrid, co-IP, and siRNA knockdown with STAT3 phosphorylation/transcription readouts

    PMID:18503751

    Open questions at the time
    • Single-lab; mechanism of how Y14 promotes STAT3 phosphorylation unclear
    • EJC dependence not resolved here
  8. 2009 Medium

    Showed MAGOH competes with STAT3 for Y14, integrating EJC assembly with signaling output.

    Evidence Endogenous co-IP and MAGOH siRNA knockdown with STAT3-dependent gene expression

    PMID:19254694

    Open questions at the time
    • Single-lab; quantitative partitioning of Y14 between EJC and STAT3 pools not determined
  9. 2011 Medium

    Linked the Y14/MAGOH heterodimer to snRNP biogenesis by showing it stimulates PRMT5-mediated Sm protein methylation, and mapped a C-terminal element controlling import and mRNA association.

    Evidence Reciprocal co-IP with methylosome, Sm methylation assays, and domain-mapping localization assays

    PMID:21209085 PMID:22355610

    Open questions at the time
    • Single-lab methylosome data
    • Magoh-independent import pathway not molecularly defined
  10. 2012 High

    Revealed Y14 as a direct inhibitor of decapping and stabilizer of mRNA, and established that RBM8A insufficiency causes TAR syndrome.

    Evidence In vitro Dcp2 decapping assays, cap-binding/mRNA half-life assays, P-body imaging; genetic and reporter analysis plus patient platelet Western blots

    PMID:22366785 PMID:23115303

    Open questions at the time
    • How decapping inhibition relates to EJC versus free Y14 not separated
    • Tissue specificity of TAR phenotype not explained mechanistically
  11. 2013 Medium

    Documented mitotic and centrosomal roles for the RBM8A-MAGOH complex and an EJC-independent function promoting NF-κB and neuronal mRNA regulation.

    Evidence siRNA cell-cycle/apoptosis assays, centrosome proximity ligation with PLK1, NF-κB reporter with RIP1/TRADD co-IP, and neuronal RNA-IP with electrophysiology

    PMID:23638902 PMID:23817415 PMID:23949737 PMID:23970407

    Open questions at the time
    • Centrosomal function molecularly unresolved
    • Single-lab signaling and behavioral data
  12. 2015 High

    Established Y14 as a regulator of neural progenitor proliferation versus differentiation through control of alternative splicing and NMD targets.

    Evidence In utero electroporation gain/loss-of-function with BrdU and genome-wide RNA-seq

    PMID:26094033

    Open questions at the time
    • Key effector splicing/NMD targets driving proliferation not individually validated
  13. 2016 High

    Pinpointed Trp-73 as the cap-binding residue separating Y14's translation-enhancement and mRNA-protection functions from its NMD activity.

    Evidence Site-directed W73V mutagenesis with cap-binding, stability, and in vitro/in vivo translation assays

    PMID:26887951

    Open questions at the time
    • How cap binding is coordinated with MAGOH-masked RRM not structurally resolved
  14. 2017 Medium

    Connected Y14 to genome-protective gene regulation by showing EJC-dependent suppression of aberrant p53 splicing and modulation of p21 and genotoxic sensitivity.

    Evidence siRNA/overexpression with RT-PCR splicing analysis, Western blot, and viability assays

    PMID:28361991

    Open questions at the time
    • Single-lab; biphasic effect of depletion vs overexpression on p53 unexplained
  15. 2019 High

    Demonstrated a direct role for Y14 in DNA double-strand break repair via ATM-dependent interaction with Ku and chromatin recruitment of DDR factors.

    Evidence IP-mass spectrometry, chromatin fractionation, γH2AX foci imaging, and DNA end-joining assays with R-loop detection

    PMID:30901577

    Open questions at the time
    • RNA-dependence of recruitment not yet mechanistically defined
    • Did not yet implicate phase separation
  16. 2020 High

    Established conserved developmental requirements for RBM8A in vertebrate neurogenesis, muscle, motor neuron, and hematopoietic development, placing it upstream of foxo3b in an NMD-controlled pathway.

    Evidence Zebrafish rbm8a mutants with epistasis (foxo3b rescue) and conditional KO mice with electrophysiology and RNA-seq

    PMID:32502192 PMID:33154347

    Open questions at the time
    • Cell-autonomous versus non-autonomous contributions not fully separated
  17. 2021 High

    Defined a Y14-p53 regulatory circuit as the basis of RBM8A's requirement in platelet production, linking the molecular pathway to the TAR phenotype.

    Evidence Megakaryocyte-specific conditional KO with Trp53 KO epistasis and pharmacological p53 inhibition

    PMID:34816104

    Open questions at the time
    • Molecular route from Y14 loss to p53 induction in megakaryocytes not detailed
  18. 2022 Medium

    Identified RBM8A as a global regulator of intronless and ribosomal protein transcript levels using acute depletion.

    Evidence CRISPR screen and auxin-degron acute depletion with genome-wide nascent transcription analysis

    PMID:36187487

    Open questions at the time
    • Single-lab; mechanism of intronless transcript regulation not defined
  19. 2023 High

    Linked Y14's repair function to biophysics, showing recombinant Y14 undergoes phosphorylation-tunable, RNA-responsive liquid-liquid phase separation that correlates with DSB repair activity.

    Evidence In vitro phase-separation assays with domain/phosphomimetic mutants, RNA titration, and DSB repair assays

    PMID:37001915

    Open questions at the time
    • Did not yet identify the kinase or co-condensing repair factors in cells
  20. 2024 Medium

    Expanded RBM8A's cytoplasmic targeted-RNA regulation, identifying circRNA/Ipo13-mediated nuclear transport and an eIF4A3 partnership stabilizing growth-signaling mRNAs.

    Evidence RNA pull-down/MS with Ipo13 co-IP in trophoblasts; co-IP, RIP-seq, and ChIP linking RBM8A/EIF4A3 to IGF1R/IRS-2 and TEAD4 regulation in breast cancer

    PMID:39232805 PMID:39413593

    Open questions at the time
    • Single-lab; generality of eIF4A3-dependent mRNA stabilization across contexts untested
  21. 2025 High

    Resolved the mechanism of Y14-dependent NHEJ, showing SRPK1 phosphorylation drives Mg2+-dependent condensates that partition Ku70/80, and extended targeted mRNA regulation to UPF3B-dependent BBC3 decay and eIF4A3-mediated EGFR stabilization supporting repair.

    Evidence Live-cell laser-damage imaging with SRPK1 inhibition and in vitro phospho-Y14 co-condensation with Ku70/80; RIP-seq, RNA pull-down, and stability assays for BBC3 and EGFR with NHEJ readouts

    PMID:40613240 PMID:40727937 PMID:41354714

    Open questions at the time
    • Single-lab cancer-context studies for BBC3/EGFR
    • How condensate-based repair integrates with canonical EJC pool unclear
  22. 2025 High

    Connected RBM8A to non-canonical Wnt/PCP signaling and intron retention control in hematopoietic and developmental contexts, and refined PYM1's role in EJC disassembly site selectivity.

    Evidence Zebrafish hypomorphs with Wnt/PCP genetic epistasis and intron-retention RNA-seq; EJC occupancy mapping with acute PYM1 depletion (preprint)

    PMID:40907933 PMID:bio_10.1101_2025.03.13.643037

    Open questions at the time
    • Direct splicing targets mediating Wnt/PCP effects not validated
    • PYM1 disassembly findings remain a preprint

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Y14 partitions between its EJC-bound pool and its many EJC-independent roles (signaling, snRNP methylation, condensate-based repair) within a single cell, and what determines target and pathway selection, remains unresolved.
  • No unifying model for context-dependent activity switching
  • Quantitative pool partitioning not measured
  • Structural basis of cap binding within the MAGOH-masked RRM unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 2 GO:0005654 nucleoplasm 2 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
DCP2EIF4A3KU70/80MAGOHNXF1PYM1STAT3UPF3B
Complex memberships
exon junction complex (EJC)methylosome (PRMT5)

Evidence

Reading pass · 39 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 in a position-specific manner, as demonstrated by microinjection of pre-mRNAs into Xenopus oocyte nuclei followed by immunoprecipitation of RNase-fragmented cytoplasmic mRNAs. Unlike Aly/REF, Y14 persists on mRNAs in the cytoplasm after nuclear export. Xenopus oocyte microinjection, immunoprecipitation of RNase-fragmented mRNAs, cytoplasmic fractionation 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 localization to the posterior pole; loss of Y14 specifically disrupts posterior oskar mRNA localization without affecting the cytoskeleton. Immunohistochemistry, genetic loss-of-function (y14 mutant oocytes), in vivo co-localization Current biology : CB High 11696323
2002 Y14 is removed from mRNAs in the cytoplasm by the process of translation; Y14 associates with monosome fractions and remains on untranslated mRNAs, but is displaced from translationally active mRNAs. Blocking translation in vivo (by strong 5' UTR secondary structure) retains Y14 on cytoplasmic mRNAs. Polysome profiling, in vitro splicing/translation-coupled reporter assay, in vivo 5' UTR secondary structure block Current biology : CB High 12121612
2003 Y14 directly interacts with hUpf3b via a conserved domain of hUpf3b, forming an NMD-activating complex. Tethered function analysis shows that the Y14/hUpf3b interaction is essential for NMD, while the hUpf3b/hUpf2 interaction is not. RNAi knockdown of Y14 impairs degradation of beta-globin NS39 NMD substrate mRNA, and Y14 is required for NMD induced by tethered hUpf3b. Tethered function assay, RNAi knockdown, co-immunoprecipitation, siRNA repletion, NMD reporter mRNA decay assay Molecular cell High 12718880
2003 Crystal structure of Drosophila Y14-Mago complex at 2.5 Å reveals that the RBD (RNA recognition motif) of Y14 engages its RNP1 and RNP2 motifs to bind Mago via protein-protein interaction rather than RNA binding. Structure-guided mutagenesis shows that the Y14-Mago association is essential for NMD function and that Mago is also a component of the NMD pathway. X-ray crystallography (2.5 Å), structure-guided mutagenesis, NMD functional assay Nature structural biology High 12730685
2003 Crystal structure of human Y14-Magoh complex shows that Magoh has an unusual flat beta-sheet structure and binds with high affinity to the RNP motif RBD of Y14, completely masking its RNA binding surface, explaining position-specific but RNA sequence-independent EJC association. X-ray crystallography (high resolution), biochemical binding assays Current biology : CB High 12781131
2003 Crystal structure of Drosophila Mago-Y14 complex at 1.85 Å shows that the canonical RNA-binding surface of the Y14 RRM is engaged in extensive protein-protein interactions with Mago, revealing molecular basis of EJC assembly. X-ray crystallography (1.85 Å) Genes & development High 12704080
2004 PYM interacts directly with Mago-Y14 by means of its N-terminal domain. Crystal structure of the Drosophila PYM-Mago-Y14 ternary complex at 1.9 Å shows PYM caps the Mago-Y14 heterodimerization interface at conserved surface residues. PYM is a cytoplasmic protein excluded from the nucleus by Crm1. Human PYM is active in NMD tethering assays. X-ray crystallography (1.9 Å), direct binding assay, nuclear exclusion/Crm1 assay, NMD tethering assay EMBO reports High 14968132
2005 Y14 is phosphorylated at its RS (arginine/serine) dipeptides, likely by SR protein-specific kinases. Phosphorylation abolishes Y14's interaction with EJC components and downstream NMD factors. A non-phosphorylatable Y14 mutant retains NMD activity but sequesters EJC/NMD factors on ribosome-containing mRNPs. Y14 is also methylated at multiple arginine residues in the C-terminal domain, and methylation is antagonized by phosphorylation of RS dipeptides. Phosphorylation mapping, SR kinase inhibition, non-phosphorylatable/phosphomimetic mutants, co-immunoprecipitation, polysome fractionation, methylation assay The Journal of biological chemistry High 16100109
2006 Y14 and nuclear export factor NXF1 form a complex in vivo that preferentially localizes within and around nuclear speckles (SC35 domains), dependent on transcription and full-length NXF1. FRAP/FLIP revealed that roughly half of accumulated BiFC complexes are immobile and this immobile fraction is depleted by ATP in permeabilized cells, indicating an ATP-dependent retention mechanism. Bimolecular fluorescence complementation (BiFC), co-immunoprecipitation with RNA, FRAP, FLIP, ATP depletion in permeabilized cells The Journal of cell biology Medium 16431928
2007 In Drosophila null clonal analysis, Tsunagi/Y14 is essential for restricting oocyte fate to a single cell; Y14 null germline cysts fail to concentrate centrosomes and oocyte-specific components in a single cell. Mago-nashi null germline stem cells fail to differentiate, and mago nashi functions independently of Y14 in germline stem cell differentiation. Null alleles, clonal analysis, immunostaining for oocyte-specific markers and centrosomes Developmental biology High 17628520
2008 Y14 was identified as a novel STAT3 binding partner via yeast two-hybrid screening. Y14 binds to STAT3 through the C-terminal region of STAT3 in vivo. siRNA-mediated knockdown of endogenous Y14 decreased IL-6-induced STAT3 tyrosine-phosphorylation, nuclear accumulation, DNA-binding activity, and STAT3-dependent gene expression. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, STAT3 phosphorylation assay, nuclear localization assay, gene expression analysis Biochemical and biophysical research communications Medium 18503751
2009 MAGOH, the Y14 partner in the EJC, inhibits STAT3-Y14 complex formation. Endogenous STAT3 co-immunoprecipitates with Y14. siRNA knockdown of MAGOH enhanced IL-6-induced STAT3-dependent gene expression, demonstrating that MAGOH regulates STAT3 transcriptional activation by interfering with the STAT3-Y14 complex. Co-immunoprecipitation, siRNA knockdown, gene expression assay Biochemical and biophysical research communications Medium 19254694
2011 Y14/Magoh heterodimer interacts with the cytoplasmic PRMT5-containing methylosome. Y14 promotes PRMT5 activity in methylation of Sm proteins of the snRNP core, and Y14 knockdown reduces Sm protein methylation. Y14 overexpression induces formation of a large, active, snRNP-associated methylosome complex. Co-immunoprecipitation (Y14/Magoh as bait), Sm methylation assay, Y14 knockdown and overexpression, complex fractionation The Journal of biological chemistry Medium 21209085
2011 Y14 contains a nuclear localization signal (YNS) that 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 can still localize to the nucleus, indicating a Magoh-independent nuclear import pathway. Deletion/mutant analysis, nuclear localization assays, spliced mRNA association assay, Magoh binding assay Scientific reports Medium 22355610
2012 Y14/Magoh heterodimer specifically associates with mRNA-decapping complex components and exoribonucleases. Y14 directly interacts with decapping factor Dcp2 and the 5' cap structure of mRNAs via different but overlapping domains. Y14 inhibits mRNA-decapping activity of Dcp2 in vitro, and Y14 overexpression prolongs reporter mRNA half-life. Y14 depletion disrupts processing body (P-body) formation, while phosphomimetic Y14 overexpression increases P-body number. Co-immunoprecipitation, in vitro decapping assay, mRNA half-life assay, siRNA depletion, overexpression of phosphomimetic mutant, P-body imaging Molecular biology of the cell High 23115303
2012 RBM8A insufficiency (compound inheritance of a null allele and regulatory SNPs in the 5' or 3' UTR of RBM8A) causes TAR syndrome. The two regulatory SNPs result in diminished RBM8A transcription in vitro, and Y14 expression is reduced in platelets from TAR individuals. In vitro transcription reporter assay, Western blot of patient platelets, genetic mapping Nature genetics High 22366785
2013 RBM8A depletion in A549 cells causes accumulation of mitotic cells, failure to progress past G2/M phase after G1/S release, increased sub-G1 population, caspase 3/7 activation, and increased frequency of multipolar or monopolar centrosomes. Silencing of either RBM8A or Magoh results in mutual downregulation of the other protein. siRNA knockdown, cell cycle analysis (flow cytometry), caspase activity assay, immunostaining of centrosomes, double thymidine block release Experimental biology and medicine (Maywood, N.J.) Medium 23970407
2013 RBM8A (Y14) and MAGOH localize to the centrosome in addition to nuclei in human A549 cells. Proximity ligation assay confirmed RBM8A-MAGOH complex formation at the centrosome. GFP-PLK1 co-localizes with Myc-RBM8A at centrosomes, suggesting RBM8A-MAGOH complex is involved in M-phase progression through direct centrosome localization. Immunostaining, proximity ligation in situ assay, tagged protein expression and co-localization, GFP-PLK1 co-localization Histochemistry and cell biology Medium 23949737
2013 Y14 positively regulates TNF-α-induced NF-κB transcriptional activity. Y14 endogenously associates with RIP1 and TRADD. Y14 lies downstream of TRADD and upstream of RIP1 in this pathway. Y14 significantly enhances the binding between RIP1 and TRADD. These actions are independent of MAGOH/EJC. siRNA knockdown, NF-κB transcriptional reporter assay, co-immunoprecipitation, epistasis by overexpression/knockdown rescue experiments Journal of immunology Medium 23817415
2015 RBM8a overexpression in embryonic cortex stimulates neural progenitor cell (NPC) proliferation and suppresses neuronal differentiation, while RBM8a knockdown reduces NPC proliferation and promotes premature differentiation. RBM8a overexpression suppresses cell cycle exit and maintains NPCs in a proliferative state. RBM8a regulates multiple alternative splicing events and NMD targets implicated in autism spectrum disorder. In utero electroporation (overexpression and knockdown), BrdU incorporation, immunostaining, genome-wide RNA-seq Neural development High 26094033
2016 An evolutionarily conserved tryptophan residue (Trp-73) of Y14 is critical for mRNA cap binding. The W73V mutant binds mRNAs weakly and fails to protect them from degradation. W73V retains partial NMD activity but cannot interact with translation initiation factors, suppresses reporter mRNA translation in vitro and in vivo, and reduces nascent protein synthesis. Thus, Trp-73 is essential for cap-binding activity and Y14-mediated translation enhancement. Site-directed mutagenesis, cap-binding assay, mRNA stability assay, co-immunoprecipitation with translation initiation factors, in vitro and in vivo translation assays The Journal of biological chemistry High 26887951
2017 Y14 depletion induces expression of an alternatively spliced p53 isoform (p53β) in human cells. Y14, in the context of the EJC, inhibits aberrant exon inclusion during p53 pre-mRNA splicing. Both depletion and overexpression of Y14 increase overall p53 protein levels. Y14 depletion reduces p21 protein levels and increases cell sensitivity to genotoxic agents. siRNA knockdown, RT-PCR splicing analysis, Western blot, cell viability/sensitivity assay, overexpression Scientific reports Medium 28361991
2018 Y14 C-terminal RS repeat-containing region controls Y14 localization: deletion or dephosphorylation-mimic mutants shift localization away from nucleoplasm, and the C-terminal RS repeat sequence itself can direct nucleolar localization. Y14 localization by the C-terminal region is further controlled by MAGOH binding. Deletion mutants, phosphomimetic/dephosphorylation-mimic mutants, fluorescence microscopy, MAGOH binding assay Scientific reports Medium 29330450
2019 Y14 depletion differentially affects expression of DNA damage response (DDR) factors and induces R-loops. Mass spectrometry after Y14 immunoprecipitation identified DDR factors as Y14-interacting partners; confirmed interactions with Ku and several DDR factors in an ATM-dependent manner. Y14 co-fractionates with Ku in chromatin-enriched fractions and accumulates on chromatin upon DNA damage. Y14 knockdown delays DDR factor recruitment to damage sites, delays γH2AX foci formation, causes Ku retention on chromatin, and compromises DNA end joining efficiency. Co-immunoprecipitation coupled with mass spectrometry, chromatin fractionation, γH2AX foci imaging, DNA end joining assay, R-loop detection, siRNA knockdown iScience High 30901577
2019 Stability of Magoh and Y14 proteins depends on their heterodimerization and nuclear localization. Interface-disrupting mutations (Magoh L136R, Y14 L118R) accelerate protein degradation without affecting mRNA levels. Y14 L118R retains nuclear localization and is more stable than Magoh L136R, which loses nuclear localization. Site-directed mutagenesis, cycloheximide chase assay, subcellular localization, Western blot, RT-PCR Biochemical and biophysical research communications Medium 30826064
2020 Homozygous zebrafish rbm8a mutations cause muscle disorganization, neural cell death, and motor neuron outgrowth defects, and dysregulate NMD targets including transcripts with 3'UTR introns (3'UI) within 50 nt downstream of stop codon. EJC-dependent NMD regulates foxo3b mRNA; loss of foxo3b function in EJC mutants significantly rescues motor axon growth defects, placing RBM8A/EJC upstream of foxo3b in a developmental signaling pathway. Zebrafish genetic mutants, RNA-seq, NMD reporter assay, genetic epistasis (foxo3b loss-of-function rescue), immunostaining PLoS genetics High 32502192
2020 Conditional knockout of Rbm8a in neural stem cells causes microcephaly, early postnatal lethality, and altered distribution of excitatory neurons. Rbm8a haploinsufficiency decreases proliferation in ganglionic eminences, reduces parvalbumin+ and neuropeptide Y+ interneurons, and decreases cortical GABA frequency. Conditional KO in NKX2.1 interneuron progenitors reduces progenitor proliferation and alters interneuron distribution. Conditional knockout mouse (neural stem cell and NKX2.1-specific), immunostaining, electrophysiology (GABA frequency), RNA-seq, BrdU proliferation assay Translational psychiatry High 33154347
2021 Megakaryocyte-specific Rbm8a knockout mice exhibit marked thrombocytopenia, internal hemorrhage, and splenomegaly. Rbm8a deficiency induces p53 and p21 in megakaryocytes. p53 inhibitor treatment or Trp53 knockout partially restores megakaryocyte differentiation and increases platelet counts, establishing a Y14-p53 regulatory circuit in platelet production. Megakaryocyte-specific conditional knockout mouse, genetic epistasis (Trp53 knockout), p53 inhibitor treatment, ex vivo megakaryocyte differentiation assay, flow cytometry iScience High 34816104
2022 RBM8A controls transcript levels of intronless genes and is a global regulator of ribosomal protein transcripts. Acute depletion of RBM8A using the auxin degron system followed by genome-wide nascent transcription analysis (SLAM-seq or equivalent) demonstrated that RBM8A regulates ribosomal protein transcript levels. CRISPR knockout screen, auxin degron acute depletion, genome-wide nascent transcription analysis, FACS-based reporter assay Frontiers in cell and developmental biology Medium 36187487
2023 Recombinant Y14 undergoes liquid-liquid phase separation (LLPS) in vitro in a manner sensitive to pH, salt concentration, and involving multivalent electrostatic interactions in low-complexity regions. Phospho-mimicry of C-terminal RS dipeptides suppresses phase separation. RNA co-phase separates into Y14 droplets in a concentration-dependent manner. LLPS capacity correlates with Y14 activity in DNA double-strand break repair. Recombinant protein phase separation assay, domain mapping, phosphomimetic mutants, RNA titration, DSB repair assay RNA (New York, N.Y.) High 37001915
2024 hsa_circ_0081343 binds directly to Rbm8a in the cytoplasm, and knockdown of hsa_circ_0081343 facilitates Rbm8a nuclear localization. Importin13 (Ipo13) recognizes Rbm8a via a functional NLS and transports it across the nuclear membrane. hsa_circ_0081343-mediated nuclear translocation of Rbm8a activates trophoblast autophagy. RNA pull-down assay, mass spectrometry, RNA immunoprecipitation, co-immunoprecipitation (Ipo13-Rbm8a), immunofluorescence, Western blot Placenta Medium 39413593
2024 RBM8A forms a complex with EIF4A3 in breast cancer cells. The RBM8A/EIF4A3 complex binds IGF1R and IRS-2 mRNA (by RIP-seq) and regulates their expression to activate the PI3K/AKT signaling pathway. TEAD4 is identified as a transcriptional activator of RBM8A by ChIP and dual luciferase reporter assays. Co-immunoprecipitation, immunofluorescence, RIP-seq, ChIP, dual-luciferase reporter assay, siRNA knockdown, xenograft Journal of translational medicine Medium 39232805
2025 SRPK1-mediated phosphorylation of Y14 is required for its localization at laser-induced DNA damage sites and function in DSB repair. Phosphorylated Y14 undergoes liquid-liquid phase separation promoted by magnesium in vitro, and Ku70/80 can partition into phosphorylated Y14 condensates. Chelation of divalent cations abolishes Y14 localization at DNA damage sites and NHEJ factor recruitment. HaloTag-Y14 live-cell imaging at laser damage sites, SRPK1 inhibition, phosphomimetic mutants, in vitro phase separation with phospho-Y14, co-condensation with Ku70/80, divalent cation chelation iScience High 40727937
2025 RBM8A promotes BBC3 (PUMA) mRNA degradation by interacting with UPF3B. RIP-seq identified BBC3 as a direct RBM8A target, confirmed by RIP-PCR, FISH-IF, and RNA pull-down. Actinomycin D assays showed RBM8A promotes BBC3 mRNA degradation. Co-immunoprecipitation confirmed RBM8A-UPF3B interaction. RIP-seq, RIP-qPCR, RNA pull-down, FISH-immunofluorescence, actinomycin D mRNA stability assay, co-immunoprecipitation International journal of molecular medicine Medium 40613240
2025 RBM8A recruits eIF4A3 to stabilize EGFR mRNA, shielding it from exonucleolytic degradation, thereby sustaining EGFR protein levels and enabling nuclear EGFR-DNA-PKcs complex formation to drive NHEJ-mediated DNA repair and suppress oxaliplatin-induced apoptosis in gastric cancer cells. siRNA screen, RIP-seq, co-immunoprecipitation (RBM8A-eIF4A3), mRNA stability assay, nuclear EGFR-DNA-PKcs interaction, NHEJ reporter, xenograft model Oncogene Medium 41354714
2025 PYM1 interaction with RBM8A/MAGOH heterodimer is required for translation-independent EJC destabilization but not for translation-dependent disassembly. EJCs lacking PYM1 interaction are enriched on non-canonical sites including intronless transcripts and transcripts with fewer and longer exons. Acute PYM1 depletion modestly inhibits NMD and stabilizes mRNAs localizing to ER-associated TIS granules. EJC occupancy mapping (iCLIP/eCLIP), acute PYM1 depletion, NMD reporter assay, RNA-seq, auxin degron system bioRxivpreprint Medium bio_10.1101_2025.03.13.643037
2025 In zebrafish, rbm8a deficiency causes accumulation of mRNAs with retained introns including non-canonical Wnt/PCP pathway components. Genetic interaction experiments show reduced rbm8a function interacts with wnt5b, wnt11f2, fzd7a, and vangl2 mutations. Rbm8a deficiency impairs lateral plate mesoderm architecture and hematopoietic gene expression (runx1, gfi1aa), connecting rbm8a to Wnt/PCP-mediated hematopoietic development. Zebrafish hypomorphic mutants, RNA-seq (intron retention), genetic epistasis with Wnt/PCP pathway mutants, live imaging of lateral plate mesoderm, in situ hybridization Developmental biology High 40907933
2013 Overexpression of RBM8a in mouse hippocampal dentate gyrus leads to increased anxiety-like behavior and abnormal social interaction. RNA immunoprecipitation (RNA-IP) detected that RBM8a binds CaMK2, GluR1, and Egr1 mRNA in neurons, and RBM8a overexpression increases miniature excitatory postsynaptic current (mEPSC) frequency. Lentiviral overexpression in vivo, behavioral tests, RNA immunoprecipitation, electrophysiology (mEPSC) Current molecular medicine Medium 23638902

Source papers

Stage 0 corpus · 72 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 328 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 186 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 147 12730685
2003 Structure of the Y14-Magoh core of the exon junction complex. Current biology : CB 104 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 55 31816601
2013 Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human cells. Experimental biology and medicine (Maywood, N.J.) 49 23970407
2019 Expression and gene regulation network of RBM8A in hepatocellular carcinoma based on data mining. Aging 48 30670676
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 45 26094033
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 45 11013075
2012 The RNA-binding protein Y14 inhibits mRNA decapping and modulates processing body formation. Molecular biology of the cell 44 23115303
2005 Phosphorylation of Y14 modulates its interaction with proteins involved in mRNA metabolism and influences its methylation. The Journal of biological chemistry 41 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 TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A. Human mutation 22 32227665
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
2022 CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA. Cell death discovery 20 35568705
2020 Full function of exon junction complex factor, Rbm8a, is critical for interneuron development. Translational psychiatry 20 33154347
2017 Y14 governs p53 expression and modulates DNA damage sensitivity. Scientific reports 20 28361991
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
2011 Specific Y14 domains mediate its nucleo-cytoplasmic shuttling and association with spliced mRNA. Scientific reports 18 22355610
2021 RBM8A Promotes Glioblastoma Growth and Invasion Through the Notch/STAT3 Pathway. Frontiers in oncology 17 34804926
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
2018 C-terminal short arginine/serine repeat sequence-dependent regulation of Y14 (RBM8A) localization. Scientific reports 14 29330450
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
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 11 34816104
1979 Familial transmission of a translocation Y/14. Human genetics 9 575349
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 6 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
2025 Rbm8a deficiency causes hematopoietic defects by modulating Wnt/PCP signaling. Developmental biology 2 40907933
2024 The Exon Junction Complex Factor RBM8A in Glial Fibrillary Acid Protein-Expressing Astrocytes Modulates Locomotion Behaviors. Cells 2 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 2 36902031
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 Phosphorylated Y14 condensates as a scaffold for DNA double-strand break repair. iScience 1 40727937
2025 RBM8A confers oxaliplatin resistance in gastric cancer by maintaining EGFR mRNA stability. Oncogene 1 41354714
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
2026 TAR syndrome causal gene RBM8A is critical for embryonic bone development and proper Hedgehog signaling. bioRxiv : the preprint server for biology 0 42079218
2026 TAR syndrome causal gene RBM8A is critical for embryonic bone development and proper Hedgehog signaling. Research square 0 42147171
2025 RBM8A promotes gastric cancer progression by binding with UPF3B to induce BBC3 mRNA degradation. International journal of molecular medicine 0 40613240
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

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