Affinage

NOL11

Nucleolar protein 11 · UniProt Q9H8H0

Length
719 aa
Mass
81.1 kDa
Annotated
2026-06-10
8 papers in source corpus 5 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NOL11 is a nucleolar protein required for ribosome biogenesis, functioning as a component of the small subunit (SSU) processome where it promotes optimal rDNA transcription and the pre-rRNA cleavage steps that generate mature 18S rRNA (PMID:22916032). It physically associates with hUTP4/Cirhin, an interaction partially disrupted by the Cirhin R565W mutation that causes North American Indian childhood cirrhosis (PMID:22916032). This ribosome biogenesis role is conserved in vertebrates: in Xenopus, Nol11 loss impairs pre-rRNA transcription and processing and triggers p53-dependent apoptosis that drives a craniofacial cartilage defect, with p53 inhibition rescuing the skeletal phenotype but not the underlying ribosome defect (PMID:25756904). Beyond ribosome assembly, NOL11 couples nucleolar function to cell cycle progression—its depletion disrupts nucleolar integrity, leading to aberrant Wee1 accumulation, increased inhibitory Cdk1 phosphorylation, and delayed mitotic entry (PMID:29881774). In mitosis NOL11 forms a trimeric NWC complex with WDR43 and Cirhin that relocates from nucleoli to perichromosomal regions, where it is required for centromeric Aurora B enrichment, histone H3 threonine-3 phosphorylation, chromosome congression, and sister chromatid cohesion (PMID:32479628). NOL11 protein stability is regulated by TAF15-mediated SUMOylation, scaffolded by the lncRNA LINC01940, which in turn enhances rDNA transcription (PMID:41402710).

Mechanistic history

Synthesis pass · year-by-year structured walk · 6 steps
  1. 2012 High

    Establishing NOL11 as an SSU processome subunit answered whether this nucleolar protein participates directly in pre-rRNA maturation and identified its physical partner.

    Evidence Yeast two-hybrid, AP-MS, and Co-IP plus siRNA knockdown with pre-rRNA processing and transcription assays in human cells

    PMID:22916032

    Open questions at the time
    • Which specific cleavage step NOL11 catalyzes or facilitates is not defined
    • No structural model of the NOL11–Cirhin interface
  2. 2012 Medium

    Showing the disease-causing Cirhin R565W mutation weakens the NOL11 interaction provided a candidate molecular basis for North American Indian childhood cirrhosis.

    Evidence Yeast two-hybrid comparison of wild-type versus R565W mutant hUTP4/Cirhin

    PMID:22916032

    Open questions at the time
    • Single-method (Y2H) interaction assay without orthogonal confirmation for the mutant
    • Functional consequence of the partial disruption on rRNA processing not quantified
  3. 2015 High

    Vertebrate loss-of-function placed NOL11 ribosome biogenesis defects upstream of p53-dependent apoptosis, explaining a tissue-specific developmental phenotype.

    Evidence Morpholino knockdown in Xenopus with pre-rRNA assays, craniofacial cartilage staining, and p53-inhibitor epistasis rescue

    PMID:25756904

    Open questions at the time
    • Why craniofacial cells are selectively sensitive is unresolved
    • p53 rescue restores skeleton but not the ribosome defect, leaving the proximal trigger of apoptosis undefined
  4. 2018 Medium

    Linking NOL11 depletion to Wee1/Cdk1 dysregulation revealed that nucleolar integrity, not checkpoint activation, governs timely mitotic entry.

    Evidence siRNA knockdown, p-Cdk1/Wee1 western blotting, actinomycin D and transcription-factor depletion controls, live-cell imaging

    PMID:29881774

    Open questions at the time
    • Mechanism connecting nucleolar disruption to Wee1 accumulation is not defined
    • Single-lab observation
  5. 2020 High

    Identifying the mitotic NWC complex established a moonlighting role for NOL11 in chromosome segregation distinct from its nucleolar function.

    Evidence Reciprocal Co-IP, immunofluorescence/live imaging, and siRNA knockdown with Aurora B localization, H3T3 phosphorylation, and segregation readouts

    PMID:32479628

    Open questions at the time
    • How the complex is targeted from nucleoli to perichromosomal regions is unknown
    • Direct molecular link between NWC and Aurora B recruitment not resolved
  6. 2025 Medium

    Discovery of TAF15-mediated SUMOylation defined a post-translational and lncRNA-scaffolded mechanism controlling NOL11 abundance and downstream rDNA transcription.

    Evidence Co-IP/MS, RNA pull-down/MS, SUMOylation and protein-stability assays, rDNA transcription assays

    PMID:41402710

    Open questions at the time
    • SUMOylation site(s) on NOL11 not mapped
    • Single-lab study without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NOL11's nucleolar ribosome-biogenesis activity and its mitotic chromosome-segregation function are mechanistically coordinated within the cell cycle remains unresolved.
  • No structural mechanism for NOL11 in any complex
  • Regulation switching NOL11 between nucleolar and perichromosomal pools unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0140098 catalytic activity, acting on RNA 2
Localization
GO:0005730 nucleolus 2 GO:0005694 chromosome 1
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-8953854 Metabolism of RNA 2
Partners
CIRH1ATAF15WDR43
Complex memberships
NWC complex (NOL11–WDR43–Cirhin)SSU processome

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 NOL11 is a component of the human ribosomal small subunit (SSU) processome, physically interacting with hUTP4/Cirhin (identified by yeast two-hybrid screening of a human liver cDNA library, affinity purification/mass spectrometry, and co-immunoprecipitation). NOL11 is required for the cleavage steps that generate mature 18S rRNA and for optimal rDNA transcription; its depletion also causes abnormal nucleolar morphology. Yeast two-hybrid, affinity purification/mass spectrometry, co-immunoprecipitation, siRNA knockdown with pre-rRNA processing and transcription assays PLoS genetics High 22916032
2012 The R565W mutation in the C-terminus of hUTP4/Cirhin (causative for North American Indian childhood cirrhosis) partially disrupts its interaction with NOL11, as shown by yeast two-hybrid analysis. Yeast two-hybrid analysis with wild-type and R565W mutant hUTP4/Cirhin PLoS genetics Medium 22916032
2015 Xenopus Nol11 is required for optimal pre-rRNA transcription and processing in a vertebrate organism. Morpholino knockdown of nol11 in Xenopus causes impaired pre-rRNA transcription and processing, increased apoptosis, and defective craniofacial cartilage development. Inhibition of p53 rescues the skeletal phenotype but not the ribosome biogenesis defect, demonstrating that p53-dependent apoptosis is activated downstream of ribosome impairment in craniofacial cells. Morpholino knockdown in Xenopus, pre-rRNA processing assays, p53 inhibitor rescue experiments, craniofacial cartilage staining PLoS genetics High 25756904
2018 NOL11 depletion delays mitotic entry by causing increased inhibitory phosphorylation of Cdk1 and aberrant accumulation of Wee1 kinase. This mitotic delay is secondary to nucleolar disruption caused by reduced rRNA levels, rather than to G2/M checkpoint activation or reduced protein synthesis, as it is recapitulated by depletion of rRNA transcription factors or actinomycin D treatment. siRNA knockdown, immunofluorescence, western blotting for p-Cdk1 and Wee1, actinomycin D treatment, live-cell imaging Science advances Medium 29881774
2020 NOL11 forms a trimeric protein complex (NWC complex) with WDR43 and Cirhin in mitotic cells. This complex localizes to nucleoli during interphase and translocates to perichromosomal regions during mitosis. The NWC complex is required for centromeric enrichment of Aurora B and the associated phosphorylation of histone H3 at threonine 3, and its absence impairs chromosome congression to the metaphase plate and sister chromatid cohesion. Co-immunoprecipitation, immunofluorescence/live imaging, siRNA knockdown with chromosome segregation and Aurora B localization assays, H3T3 phosphorylation western blotting Nucleic acids research High 32479628
2025 NOL11 is SUMOylated by the SUMO2 E3 ligase TAF15, and this SUMOylation enhances NOL11 protein stability, which in turn increases rDNA transcription and ribosome biogenesis. The lncRNA LINC01940 acts as a scaffold promoting the TAF15–NOL11 interaction to drive this modification. Co-immunoprecipitation mass spectrometry, RNA pull-down mass spectrometry, rDNA transcription assays, SUMOylation assays, protein stability assays Cellular & molecular biology letters Medium 41402710

Source papers

Stage 0 corpus · 8 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 NOL11, implicated in the pathogenesis of North American Indian childhood cirrhosis, is required for pre-rRNA transcription and processing. PLoS genetics 81 22916032
2015 The ribosome biogenesis factor Nol11 is required for optimal rDNA transcription and craniofacial development in Xenopus. PLoS genetics 38 25756904
2020 Identification of a novel nucleolar protein complex required for mitotic chromosome segregation through centromeric accumulation of Aurora B. Nucleic acids research 20 32479628
2018 Nucleolar integrity during interphase supports faithful Cdk1 activation and mitotic entry. Science advances 17 29881774
2018 Comprehensive analysis of coexpressed long noncoding RNAs and genes in breast cancer. The journal of obstetrics and gynaecology research 16 30362198
2020 Constructing a 10-core genes panel for diagnosis of pediatric sepsis. Journal of clinical laboratory analysis 13 33274532
2020 Genetic Signatures of Acute Asthma Exacerbation Related With Ineffective Response to Corticosteroid. Allergy, asthma & immunology research 5 32400129
2025 The cancer-testis lncRNA LINC01940 promotes gastric cancer malignant progression and chemoresistance by enhancing ribosome biogenesis via TAF15-mediated NOL11 SUMOylation. Cellular & molecular biology letters 0 41402710

Missed literature

Know a paper Affinage missed for NOL11? Flag it for the maintainers and the community.

No submissions yet.