Affinage

RBM26

RNA-binding protein 26 · UniProt Q5T8P6

Length
1007 aa
Mass
113.6 kDa
Annotated
2026-06-10
19 papers in source corpus 7 papers cited in narrative 8 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RBM26 is a nuclear RNA-binding protein that governs the fate of nuclear polyadenylated RNAs by coupling transcript features to exosome-mediated decay and to splicing of terminal introns (PMID:31950173, PMID:37661812). As a limiting, transient component of the PAXT connection (with RBM27, ZC3H3, and PABPN1), RBM26 is recruited to the 3' ends of short, exon-poor polyadenylated RNAs, where it cooperates with ZC3H3 to trigger 'opening' of the core PAXT factor ZFC3H1 from its co-transcriptionally loaded closed conformation, thereby licensing exosomal degradation and steering transcripts away from export (PMID:31950173, PMID:39461342). In a distinct branch, RBM26 is recruited by PABPN1 to promote splicing of last introns bearing weak 3' splice sites (PMID:37661812). Studies of the C. elegans ortholog rbm-26 establish a direct post-transcriptional repressor role: it binds mals-1 (MALSU1) mRNA to limit expression of this mitoribosomal assembly factor, protecting developing neurons from mitochondrial dysfunction and axon degeneration; autism-associated missense variants destabilize the protein and recapitulate these axonal defects (PMID:39480871).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2017 Low

    Established that RBM26 carries arginine methylation, raising the question of whether its RG repeats are post-translationally regulated.

    Evidence Immunoprecipitation with an MMA-RG-repeat-specific antibody and mass spectrometry in EBV-transformed B-cells

    PMID:28758620

    Open questions at the time
    • Single Co-IP/MS identification with no functional follow-up on RBM26 specifically
    • Methyltransferase responsible and functional consequence of methylation unknown
  2. 2020 High

    Placed RBM26 in the nuclear RNA decay machinery by identifying it as a limiting component of the PAXT connection required for exosomal degradation of polyadenylated RNA.

    Evidence Nuclear pA+-RNA proteome characterization, MTR4-ZFC3H1 co-complex purification, and loss-of-function with substrate accumulation readout

    PMID:31950173

    Open questions at the time
    • Direct RNA target spectrum of RBM26 within PAXT not defined
    • Whether RBM26 and RBM27 act redundantly or distinctly unresolved
  3. 2023 Medium

    Revealed a non-decay function: PABPN1 recruits RBM26/27 to promote splicing of terminal introns with weak 3' splice sites, expanding its role beyond degradation.

    Evidence PABPN1 depletion with intron retention readout, TurboID-MS interactome, tethering assay, and domain mapping

    PMID:37661812

    Open questions at the time
    • RBM26-specific (vs RBM27) contribution to splicing not separated
    • Mechanism by which weak 3' splice sites are selected is unclear
  4. 2024 High

    Defined how RBM26 acts mechanistically within PAXT, showing it (with ZC3H3) is recruited to 3' ends of short RNAs to trigger ZFC3H1 conformational opening that commits transcripts to decay.

    Evidence Functional dissection of ZFC3H1 closed/open states with RBM26/27 and ZC3H3 depletion and co-transcriptional loading assays

    PMID:39461342

    Open questions at the time
    • Structural basis of RBM26-induced ZFC3H1 opening not resolved
    • Features beyond exon number that mark a transcript for RBM26 recruitment undefined
  5. 2024 High

    Demonstrated a direct, conserved post-transcriptional repressor activity: the ortholog rbm-26 binds mals-1 mRNA to limit MALSU1 expression and protect neurons from mitochondrial dysfunction and axon degeneration, and disease-associated variants destabilize the protein to recapitulate defects.

    Evidence Biochemical mRNA-binding screen, C. elegans loss-of-function and missense-variant genetics, epistasis, and protein/mRNA quantification (peer-reviewed plus corresponding preprint)

    PMID:37873356 PMID:39480871

    Open questions at the time
    • Whether human RBM26 represses MALSU1 mRNA equivalently not shown
    • Connection between mRNA repression and the PAXT/splicing functions unestablished

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RBM26's three reported activities—PAXT-mediated decay, terminal-intron splicing, and direct mRNA target repression—are integrated within one protein, and whether they share an RNA-binding determinant, remains open.
  • No unified model linking decay, splicing, and target-specific repression
  • Human RBM26 RNA target set not directly mapped
  • Functional role of RG-repeat arginine methylation in any of these activities unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-8953854 Metabolism of RNA 3
Complex memberships
PAXT connection

Evidence

Reading pass · 8 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2020 RBM26 (along with RBM27, ZC3H3, and PABPN1) is a component of the PAXT (Poly(A) Tail eXosome Targeting) connection required for nuclear RNA exosome-mediated degradation of polyadenylated RNA. Loss of RBM26 results in accumulation of PAXT substrates, establishing it as a limiting factor for PAXT activity. Characterization of nuclear pA+-RNA bound proteomes, MTR4-ZFC3H1 co-complex purification, knockdown/loss-of-function with substrate accumulation readout Nucleic acids research High 31950173
2024 ZFC3H1 (core PAXT component) adopts a 'closed' conformation when initially loaded co-transcriptionally, blocking exosome recruitment. Short RNAs with fewer exons preferentially recruit transient PAXT components ZC3H3 and RBM26/27 to the 3' end, which triggers ZFC3H1 'opening' and subsequent exosomal degradation, thereby determining RNA fate between export and decay. Functional dissection of ZFC3H1 conformational states, depletion of RBM26/27 and ZC3H3 with RNA fate readouts, co-transcriptional loading assays Molecular cell High 39461342
2023 PABPN1 recruits RBM26 and RBM27 to promote splicing of last introns with weak 3' splice sites; this interaction involves the coiled-coil and RRM domain of RBM27 (and by extension RBM26), and tethering PABPN1 to non-polyadenylated transcripts is sufficient to promote splicing, indicating a direct role. PABPN1 depletion with intron retention readout, TurboID-MS interactome, tethering assay, domain interaction mapping EMBO reports Medium 37661812
2024 In C. elegans, rbm-26 (ortholog of human RBM26/RBM27) encodes an RNA-binding protein that negatively regulates expression of the MALS-1 (MALSU1) mitoribosomal assembly factor by binding its mRNA. Loss of rbm-26 causes dramatic overexpression of mals-1 mRNA and MALS-1 protein, leading to mitochondrial dysfunction and axon degeneration during larval neurodevelopment; genetic epistasis shows MALS-1 overexpression is responsible for these defects. Biochemical mRNA-binding screen, C. elegans loss-of-function genetics, genetic epistasis (double mutant rescue), protein and mRNA quantification PLoS biology High 39480871
2024 Autism-associated missense variants in C. elegans rbm-26 (RBM26/27 ortholog) cause a sharp decrease in RBM-26 protein expression and produce axon overlap and axon degeneration phenotypes during larval development, mechanistically linking disease-associated variants to loss of RBM-26 protein stability and downstream MALS-1 dysregulation. Missense variant introduction in C. elegans, protein expression quantification, axon morphology phenotyping PLoS biology Medium 39480871
2024 Preprint version confirms rbm-26 (C. elegans RBM26/27 ortholog) binds mals-1 mRNA and negatively regulates its expression; loss of rbm-26 overexpresses MALS-1 and causes mitochondrial and axon degeneration defects reversed by reducing mals-1, consistent with the published peer-reviewed findings. Biochemical screen, genetics, mRNA/protein quantification in C. elegans bioRxivpreprint Medium 37873356
2025 In fission yeast S. japonicus, the RBM26/27 ortholog Rmn1 interacts with Pab2/PABPN1 and participates in constitutive heterochromatin formation at centromeres; Rmn1 can also interact with the H3K9 methyltransferase Clr4, placing it in a complex required for heterochromatin assembly. Co-immunoprecipitation, genetic deletion analysis (Pab2 N-terminal deletion disrupting interaction), chromatin/histone methylation assays at centromeres PLoS genetics Medium 40163528
2017 RBM26 was identified as a mono-methylated arginine (MMA)-containing protein in EBV-transformed B-cells, co-immunoprecipitated using an MMA-RG-repeat-specific antibody and confirmed by immunoprecipitation and/or Western blot, indicating RBM26 harbors MMA post-translational modifications on its RG repeat sequences. Immunoprecipitation with MMA-specific monoclonal antibody, mass spectrometry, Western blot confirmation The Journal of general virology Low 28758620

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Adenovirus-mediated intralesional interferon-gamma gene transfer induces tumor regressions in cutaneous lymphomas. Blood 87 15161670
2020 The human ZC3H3 and RBM26/27 proteins are critical for PAXT-mediated nuclear RNA decay. Nucleic acids research 62 31950173
2016 Molecular and Biochemical Characterization of a Novel Xylanase from Massilia sp. RBM26 Isolated from the Feces of Rhinopithecus bieti. Journal of microbiology and biotechnology 33 26387816
2023 The polyA tail facilitates splicing of last introns with weak 3' splice sites via PABPN1. EMBO reports 23 37661812
2019 Characterization of a novel salt-, xylose- and alkali-tolerant GH43 bifunctional β-xylosidase/α-l-arabinofuranosidase from the gut bacterial genome. Journal of bioscience and bioengineering 17 31109875
2012 Genome-wide profiling of pluripotent cells reveals a unique molecular signature of human embryonic germ cells. PloS one 17 22737227
2018 Association Analysis Identifies New Risk Loci for Coal Workers' Pneumoconiosis in Han Chinese Men. Toxicological sciences : an official journal of the Society of Toxicology 16 29394417
2021 Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder. Frontiers in molecular biosciences 13 34746237
2017 Antibodies against the mono-methylated arginine-glycine repeat (MMA-RG) of the Epstein-Barr virus nuclear antigen 2 (EBNA2) identify potential cellular proteins targeted in viral transformation. The Journal of general virology 10 28758620
2024 Genome-Wide Association Study Meta-Analysis of 9619 Cases With Tic Disorders. Biological psychiatry 8 39389409
2024 Dual modes of ZFC3H1 confer selectivity in nuclear RNA sorting. Molecular cell 6 39461342
2022 Identification of ceRNA regulatory network in acute pancreatitis and acute recurrent pancreatitis. European journal of gastroenterology & hepatology 5 36052691
2025 A putative lncRNA RBM26-AS1-encoded micropeptide promotes colon cancer progression. International journal of surgery (London, England) 4 40652529
2024 Ortholog of autism candidate gene RBM27 regulates mitoribosomal assembly factor MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment. PLoS biology 4 39480871
2015 13q31.1 microdeletion: A prenatal case report with macrocephaly and macroglossia. European journal of medical genetics 3 26365529
2025 Glutathiones' life in multi-cancers: especially their potential micropetides in liver hepatocellular carcinoma. Discover oncology 1 39966283
2025 Identification of the Lynch syndrome and Lynch-like syndrome specific somatic mutations in microsatellite instability-high colorectal cancer cases. Surgery today 1 41441884
2025 The nuclear poly(A)-binding protein Pab2/PABPN1 promotes heterochromatin assembly through the formation of Pab2 nuclear condensates. PLoS genetics 0 40163528
2024 Autism candidate gene rbm-26 (RBM26/27) regulates MALS-1 to protect against mitochondrial dysfunction and axon degeneration during neurodevelopment. bioRxiv : the preprint server for biology 0 37873356

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