Affinage

NOL10

Nucleolar protein 10 · UniProt Q9BSC4

Round 2 corrected
Length
688 aa
Mass
80.3 kDa
Annotated
2026-04-29
46 papers in source corpus 7 papers cited in narrative 7 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOL10 is a nucleolar scaffold protein that assembles with AATF and NGDN into the trimeric ANN complex via its WD40 repeats, and this complex is essential for 18S rRNA maturation and 40S ribosomal subunit biogenesis (PMID:27599843, PMID:41093997). As an intrinsically disordered protein, NOL10 constitutes the skeletal granule meshwork of the nucleolar granular component, remains anchored in the nucleolus under osmotic stress, and serves as a platform for reassembly of other nucleolar proteins after stress; sequestration by polyglutamine-expanded proteins causes pathological nucleolar deformity (PMID:36599853). A homozygous WD40-domain missense mutation (p.Asn228His) abolishes AATF/NGDN interaction, mislocalizes NOL10 to the nucleoplasm, impairs 40S subunit production, and causes G0/G1 arrest and cell death in patient fibroblasts, establishing NOL10 deficiency as a cause of a ribosomopathy (PMID:41093997). NOL10 also physically interacts with the DDX10 moiety of the NUP98::DDX10 leukemia fusion protein, and its loss impairs leukemia progression in a mouse model (PMID:40263434).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2014 Medium

    Establishing NOL10 as a stably incorporated nucleolar component resolved its subnuclear address and raised the question of what macromolecular complex it participates in.

    Evidence GFP-NOL10 live-cell imaging and FRAP in HeLa cells showed nucleolar localization (DFC/GC) and very low mobility indicating tight complex association

    PMID:24754225

    Open questions at the time
    • Identity of the complex(es) retaining NOL10 in the nucleolus was unknown
    • Functional role in rRNA processing not yet tested
  2. 2016 High

    Identification of the ANN complex (NOL10–AATF–NGDN) and its requirement for 18S rRNA maturation defined NOL10's molecular function in ribosome biogenesis and showed that its WD40 repeats mediate complex assembly.

    Evidence Reciprocal co-IP, domain-mapping mutagenesis, siRNA knockdown with Northern blot rRNA processing assays in human cells

    PMID:27599843

    Open questions at the time
    • Structural basis of ANN complex assembly unresolved
    • Whether NOL10 has functions beyond rRNA processing not addressed
    • No in vivo disease model yet linked to ANN disruption
  3. 2023 High

    Biophysical characterization revealed that NOL10 is an intrinsically disordered protein forming the granular-component meshwork and acting as a nucleolar stress anchor, explaining its scaffold role and linking its sequestration to polyglutamine disease pathology.

    Evidence HS-AFM, STED super-resolution, CLEM, droplet assays, osmotic stress live imaging, and polyglutamine disease cell models

    PMID:36599853

    Open questions at the time
    • Molecular determinants of stress-resistant anchoring are not mapped
    • Causal role in polyglutamine disease progression not demonstrated in animal models
  4. 2025 High

    A patient-derived WD40 missense variant (N228H) proved that ANN complex integrity is essential for human 40S subunit production and cell viability, establishing NOL10 deficiency as a ribosomopathy.

    Evidence Exome sequencing, immunofluorescence, co-IP, polysome profiling, and cell cycle analysis in patient fibroblasts

    PMID:41093997

    Open questions at the time
    • Full clinical spectrum and prevalence of NOL10-associated disease remain undefined
    • Whether residual NOL10 function persists or variant is a complete loss-of-function is unclear
  5. 2025 Medium

    Discovery that NOL10 physically interacts with the NUP98::DDX10 oncofusion and is a critical dependency for leukemia progression expanded NOL10's relevance beyond normal ribosome biogenesis into oncogenic mechanisms.

    Evidence Co-IP domain mapping, Nol10-knockout mouse leukemia model with survival analysis, ATF4 mRNA stability and serine biosynthesis pathway analysis

    PMID:40263434

    Open questions at the time
    • Whether the leukemia dependency reflects canonical ribosome biogenesis or a neomorphic function is unresolved
    • Therapeutic vulnerability of the NOL10–DDX10 interaction not tested
  6. 2025 Medium

    A prostate cancer risk SNP at the NOL10 locus was shown to increase NOL10 transcription via allele-specific USF1 binding, and NOL10 overexpression promoted cell cycle progression, linking NOL10 dosage to cancer proliferation.

    Evidence SNPs-seq, allele-specific proteomics, functional cell cycle assays in prostate cancer cells

    PMID:41062477

    Open questions at the time
    • Whether cell cycle effects are mediated through ribosome biogenesis or an independent pathway is unclear
    • In vivo validation of NOL10 overexpression driving tumor growth is lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic structure of the ANN complex, the mechanism by which NOL10's intrinsic disorder confers stress-resistant nucleolar anchoring, and whether NOL10's roles in leukemia and prostate cancer are ribosome biogenesis-dependent or involve distinct moonlighting functions.
  • No high-resolution structure of the ANN complex or NOL10 alone
  • Mechanistic basis of stress-resistant anchoring not mapped to specific disordered regions
  • Ribosome biogenesis-dependent vs. independent contributions to cancer biology not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0003723 RNA binding 1
Localization
GO:0005730 nucleolus 3 GO:0005634 nucleus 2
Pathway
R-HSA-1643685 Disease 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-8953854 Metabolism of RNA 2
Partners
AATFNGDNNUP98::DDX10USF1
Complex memberships
ANN complex (NOL10–AATF–NGDN)

Evidence

Reading pass · 7 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2016 NOL10 forms a salt-stable trimeric protein complex with AATF and NGDN (the ANN complex) in human cells. All three subunits localize to nucleoli and show mutual dependence for protein stability. The WD40 repeats of NOL10 and the UTP3/SAS10 domain of NGDN are required for complex formation. The ANN complex is required for nucleolar steps of 40S ribosomal subunit biosynthesis, specifically for 18S rRNA maturation; depletion of any single member affects the same cleavage steps in the 5'ETS and ITS1 regions of the ribosomal RNA precursor. Immunoprecipitation, domain-mapping mutagenesis, siRNA knockdown, rRNA processing assays (Northern blot), nucleolar localization by microscopy Nucleic acids research High 27599843
2023 PQBP5/NOL10 is an intrinsically disordered protein that constitutes the skeletal granule meshwork of the granular component of the nucleolus (distinct from the fibrillar center and dense fibrillar component). Unlike other nucleolar proteins that disperse to the nucleoplasm under osmotic stress, NOL10 remains in the nucleolus and functions as an anchor for reassembly of other nucleolar proteins after stress. Its biophysical properties remain stable under stress conditions. In polyglutamine disease models, NOL10 is sequestered by polyglutamine proteins, leading to pathological nucleolar deformity. High-speed atomic force microscopy (HS-AFM), super-resolution microscopy (STED), correlative light-electron microscopy (CLEM), droplet assay, thermal shift assay, osmotic stress experiments with live imaging Nature communications High 36599853
2014 GFP-NOL10 localizes to the dense fibrillar component and granular component of nucleoli in living HeLa cells. Its mobility is very low under normal conditions, indicating tight binding to macroprotein complexes, consistent with a scaffold or core role. When rRNA transcription is suppressed, mobility increases but remains slow. GFP-fusion live-cell imaging, FRAP in living cells, suppression of rRNA transcription by ActD treatment Biochemistry and cell biology Medium 24754225
2025 A homozygous missense variant in the WD-repeat domain of NOL10 (p.Asn228His) causes nucleoplasmic mislocalization of the NOL10 protein, loss of interaction with AATF and NGDN, specific impairment of 40S ribosomal subunit maturation (reduced 40S, 80S, and polysome content), G0/G1 cell cycle arrest, and increased cell death in patient-derived fibroblasts. Structural modeling predicts N228H is strongly destabilizing. Exome sequencing, immunofluorescence (localization), co-immunoprecipitation (interaction loss), polysome profiling, cell cycle analysis, structural modeling and ΔΔG calculations Journal of human genetics High 41093997
2025 NOL10 physically interacts with a 24-amino-acid region within the DDX10 moiety of the NUP98::DDX10 leukemia fusion protein. NOL10 is a critical dependency of NUP98::DDX10 leukemia; loss of Nol10 in a mouse model impairs disease progression and improves survival. NOL10 acts cooperatively with NUP98::DDX10 to regulate the serine biosynthesis pathway and stabilize ATF4 mRNA. Co-immunoprecipitation (interaction mapping), mouse leukemia model (Nol10 knockout), gene expression analysis (serine biosynthesis pathway), mRNA stability assays (ATF4) Leukemia Medium 40263434
2025 The risk allele A of rs4519489 (in the NOL10 locus) exhibits enhanced binding to the transcription factor USF1, resulting in elevated NOL10 expression. NOL10 overexpression promotes cell cycle progression in prostate cancer cells. USF1 thus regulates NOL10 transcription through allele-specific binding at the 2p25 locus. SNPs-seq (allele-specific protein binding), unbiased proteomics (allele-specific capture), functional cell cycle assays, clinical cohort correlation Nature communications Medium 41062477
2025 In fission yeast, Enp2/NOL10 forms a complex with a novel non-coding RNA (RiboCop) and RNase H1 in response to improper pre-rRNA processing by Dicer during quiescence. This complex triggers rDNA repeat silencing via Sir2, RENT, and H3K9 methylation specifically during cellular dormancy. RNA co-immunoprecipitation, genetic mutant analysis (Dicer mutants), chromatin immunoprecipitation, epistasis analysis (Sir2/RENT/H3K9me pathway) bioRxivpreprint Low 41000809

Source papers

Stage 0 corpus · 46 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 3411 32353859
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2012 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts. Molecular cell 973 22681889
2002 Directed proteomic analysis of the human nucleolus. Current biology : CB 780 11790298
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2018 High-Density Proximity Mapping Reveals the Subcellular Organization of mRNA-Associated Granules and Bodies. Molecular cell 580 29395067
2020 Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.) 564 33060197
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2002 Functional proteomic analysis of human nucleolus. Molecular biology of the cell 391 12429849
2014 A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer. Nature genetics 362 25217961
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2018 Mapping the Genetic Landscape of Human Cells. Cell 225 30033366
2017 Optimized fragmentation schemes and data analysis strategies for proteome-wide cross-link identification. Nature communications 221 28524877
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2019 H4K20me0 recognition by BRCA1-BARD1 directs homologous recombination to sister chromatids. Nature cell biology 162 30804502
2015 BioID-based Identification of Skp Cullin F-box (SCF)β-TrCP1/2 E3 Ligase Substrates. Molecular & cellular proteomics : MCP 149 25900982
2020 A High-Density Human Mitochondrial Proximity Interaction Network. Cell metabolism 148 32877691
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2022 PHGDH Inhibits Ferroptosis and Promotes Malignant Progression by Upregulating SLC7A11 in Bladder Cancer. International journal of biological sciences 143 36147463
2016 FOXA1 Directs H3K4 Monomethylation at Enhancers via Recruitment of the Methyltransferase MLL3. Cell reports 137 27926873
2018 Circular RNA circNOL10 Inhibits Lung Cancer Development by Promoting SCLM1-Mediated Transcriptional Regulation of the Humanin Polypeptide Family. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 87 30693177
2022 Methylation Pattern Mediated by m6A Regulator and Tumor Microenvironment Invasion in Lung Adenocarcinoma. Oxidative medicine and cellular longevity 30 35035657
2016 Human AATF/Che-1 forms a nucleolar protein complex with NGDN and NOL10 required for 40S ribosomal subunit synthesis. Nucleic acids research 23 27599843
2023 PQBP5/NOL10 maintains and anchors the nucleolus under physiological and osmotic stress conditions. Nature communications 19 36599853
2021 circ-NOL10 regulated by MTDH/CASC3 inhibits breast cancer progression and metastasis via multiple miRNAs and PDCD4. Molecular therapy. Nucleic acids 19 34729247
2014 Dynamics of WD-repeat containing proteins in SSU processome components. Biochemistry and cell biology = Biochimie et biologie cellulaire 16 24754225
2023 Expression status of circ-SMARCA5, circ-NOL10, circ-LDLRAD3, and circ-RHOT1 in patients with colorectal cancer. Scientific reports 10 37587156
2019 Exome sequencing in genomic regions related to racing performance of Quarter Horses. Journal of applied genetics 9 30666567
2025 NOL10 variant disrupts ribosome biogenesis and underlies hippocampal sclerosis. Journal of human genetics 5 41093997
2019 Integrative omics analysis identifies macrophage migration inhibitory factor signaling pathways underlying human hepatic fibrogenesis and fibrosis. Journal of bio-X research 5 32953199
2025 Loss of NOL10 leads to impaired disease progression of NUP98::DDX10 leukemia. Leukemia 2 40263434
2025 Combined SNPs sequencing and allele specific proteomics capture reveal functional causality underpinning the 2p25 prostate cancer susceptibility locus. Nature communications 2 41062477
2024 Combined SNPs sequencing and allele specific proteomics capture reveal functional causality underpinning the 2p25 prostate cancer susceptibility locus. Research square 2 38645058
2026 Diagnostic Utility of Expression Imbalance in the Idylla GeneFusion Assay for Non-Small-Cell Lung Cancer. The Journal of molecular diagnostics : JMD 0 41763606
2025 RiboCop surveils pre-rRNA processing by Dicer in cellular quiescence. bioRxiv : the preprint server for biology 0 41000809
2024 PQBP3/NOL7 is an intrinsically disordered protein. Biochemical and biophysical research communications 0 39126896