Affinage

SURF6

Surfeit locus protein 6 · UniProt O75683

Length
361 aa
Mass
41.5 kDa
Annotated
2026-04-28
19 papers in source corpus 13 papers cited in narrative 13 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SURF6 is an intrinsically disordered nucleolar matrix protein essential for ribosome biogenesis and cell proliferation. It resides in the granular component of the nucleolus, preferentially binds RNA, and stabilizes pre-rRNA intragenic transcribed spacers (particularly ITS2) while regulating the choice between the two mammalian pre-rRNA processing pathways in a p53-independent manner (PMID:21063453, PMID:37450438). Electrostatic interactions between the disordered regions of SURF6 and NPM1 drive liquid–liquid phase separation that organizes nucleolar sub-phases, with SURF6/rRNA-rich cores releasing assembled ribosomal subunits to NPM1-rich shells for nucleolar efflux (PMID:30498217). Beyond the nucleolus, SURF6 inhibits IRF7 nuclear translocation and thereby suppresses IFNβ production downstream of KRAS/miR-3655 signaling (PMID:39523457).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1996 Medium

    Establishing SURF6 as a nucleolar protein localized to the granular component provided the first subcellular context for its function in ribosome maturation.

    Evidence Immunofluorescence and immunoblot in mammalian cells

    PMID:8639267

    Open questions at the time
    • No functional data; localization alone does not specify role in ribosome biogenesis
  2. 1998 High

    Demonstrating that SURF6 is a nucleolar matrix component that binds RNA preferentially over DNA, and co-localizes with NPM1/B23 and fibrillarin, defined it as an RNA-associated structural nucleolar protein.

    Evidence Nucleolar subfractionation, in vitro nucleic acid binding with recombinant protein, double immunolabeling

    PMID:9548374

    Open questions at the time
    • Specific RNA targets not identified
    • No loss-of-function data
  3. 2005 Medium

    Identification of an evolutionarily conserved SURF-6 domain with multiple independent nucleolar targeting regions, and confirmation that SURF6 associates with RNA (not DNA) in situ, established it as a conserved nucleolar RNA-binding factor involved in late ribosome assembly steps.

    Evidence GFP-fusion localization and deletion mapping; in situ RNase/DNase sensitivity combined with cell cycle immunofluorescence

    PMID:15629442 PMID:16363129

    Open questions at the time
    • Functional consequence of domain deletions unknown
    • No direct rRNA processing data
  4. 2006 High

    Loss-of-function studies showed SURF6 is essential for mammalian cell viability, cell cycle progression (G1 arrest), and preimplantation development, with knockdown reducing 18S rRNA levels and causing embryonic arrest.

    Evidence RNAi in mouse embryos with qRT-PCR for rRNA; conditional antisense in NIH/3T3 with flow cytometry

    PMID:16855206 PMID:17086444

    Open questions at the time
    • Mechanism linking SURF6 loss to reduced 18S unclear
    • Whether cell death is a direct ribosome biogenesis defect or secondary stress response not resolved
  5. 2010 Medium

    Overexpression of SURF6 stabilized ITS2 and 5′ETS pre-rRNA spacers without altering mature rRNA, revealing a direct role in preventing premature spacer cleavage analogous to yeast Rrp14.

    Evidence Doxycycline-inducible overexpression in NIH/3T3, dot-hybridization with biotinylated probes

    PMID:21063453

    Open questions at the time
    • Overexpression only; no complementary knockdown rRNA processing data at this time
    • Direct RNA binding to spacer sequences not shown
  6. 2014 Medium

    Identification of NPM1/B23, nucleolin, EBP2, and UBF as SURF6-interacting partners placed SURF6 at the intersection of rDNA transcription and rRNA processing.

    Evidence GST pull-down followed by mass spectrometry in HeLa cells

    PMID:25898752

    Open questions at the time
    • No reciprocal co-IP validation
    • Functional significance of individual interactions not tested
  7. 2017 High

    Demonstrating that SURF6 overexpression accelerates proliferation and shortens G1 by ~30% while accumulating rRNA intermediates from both subunit maturation pathways established SURF6 as a positive regulator of G1/S transition coupled to rRNA processing.

    Evidence Tet-On overexpression, real-time proliferation monitoring, flow cytometry, BrdU labeling, Northern blot in NIH/3T3

    PMID:28873013

    Open questions at the time
    • Causal link between rRNA processing and G1/S transition not mechanistically dissected
    • Whether effect on proliferation is cell-type specific unknown
  8. 2018 High

    Reconstituting NPM1–SURF6 liquid–liquid phase separation in vitro revealed that electrostatic interactions between their disordered regions drive nucleolar-like condensate formation, establishing a biophysical basis for nucleolar organization.

    Evidence In vitro phase separation reconstitution with fluorescence microscopy and quantitative biophysical characterization

    PMID:30498217

    Open questions at the time
    • In vitro system lacks rRNA; role of RNA in modulating phase behavior not addressed
    • In vivo validation of interconverting scaffolding networks not performed
  9. 2023 High

    Bidirectional manipulation (knockdown and overexpression) in multiple cell lines showed SURF6 regulates the choice between pre-rRNA processing pathways 1 and 2 in a p53-independent manner, resolving its specific role in rRNA maturation.

    Evidence siRNA and overexpression in HeLa and HCT116 cells, Northern blot/RT-PCR of rRNA precursors, flow cytometry, p53-null cell lines

    PMID:37450438

    Open questions at the time
    • How SURF6 mechanistically shifts pathway choice is unknown
    • Whether pathway shift underlies proliferative phenotype not tested
  10. 2024 Medium

    Placing SURF6 in a KRAS–miR-3655–SURF6–IRF7–IFNβ axis revealed an extranucleolar function in innate immune signaling, where SURF6 inhibits IRF7 nuclear translocation.

    Evidence miRNA target validation, nuclear fractionation, IFNβ promoter assays, loss-of-function experiments

    PMID:39523457

    Open questions at the time
    • Mechanism by which SURF6 retains IRF7 in cytoplasm unknown
    • Whether this function is independent of nucleolar roles unresolved
    • Single-lab finding not yet replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanism by which SURF6 switches pre-rRNA processing pathway choice, the structural basis of SURF6–rRNA interactions, and whether its innate immune regulatory function is physiologically separable from its nucleolar role remain open questions.
  • No structural model of SURF6 or its RNA-binding mode
  • Specific rRNA sequences bound by SURF6 not mapped
  • In vivo validation of multiphase condensate assembly-line model pending peer review

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005730 nucleolus 4 GO:0005634 nucleus 2
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 1
Partners
EBP2IRF7NCLNPM1UBF

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 SURF6 is a novel nucleolar protein localized predominantly in the granular component of the nucleolus, a structure involved in ribosome maturation, as determined by immunofluorescence and immunoblot analyses. Immunofluorescence, immunoblot analysis DNA and cell biology Medium 8639267
1998 SURF6 is a component of the nucleolar matrix and binds both DNA and RNA in vitro, with stronger preference for RNA; it co-localizes with B23 and fibrillarin in interphase and at perichromosomal layers during mitosis. Immunofluorescence, immunoblot of nucleolar subfractions, in vitro nucleic acid binding assay with endogenous and recombinant SURF6, double immunolabeling European journal of cell biology High 9548374
2005 An evolutionarily conserved SURF-6 domain is present in the carboxy-terminus of a family of eukaryotic nucleolar proteins; GFP-fusion experiments showed proteins from distantly related species containing this domain localize to the nucleolus; deletion analysis showed multiple regions of SURF6 can independently target to the nucleolus. GFP fusion protein localization, deletion analysis, bioinformatic domain identification Biochemical and biophysical research communications Medium 15629442
2005 In interphase mouse NIH/3T3 cells, SURF6 is associated with RNA (not DNA) in situ; during mitosis SURF6 appears in forming nucleoli after fibrillarin and B23, suggesting involvement in terminal stages of ribosomal particle assembly. Immunofluorescence with RNase A and DNase I treatment in situ, cell cycle synchronization and immunoblot Bioorganicheskaia khimiia Medium 16363129
2006 Knockdown of Surf6 mRNA by RNAi in mouse preimplantation embryos caused developmental arrest at the 8-cell/morula stage and decreased 18S rRNA levels, demonstrating that SURF6 is essential for preimplantation development and ribosome biogenesis. RNAi knockdown, immunocytochemistry, qRT-PCR for rRNA levels Biology of reproduction High 16855206
2006 Conditional antisense RNA-mediated depletion of SURF6 in NIH/3T3 cells caused cell death and apparent G1 phase arrest, demonstrating SURF6 is essential for mammalian cell viability and cell cycle progression. Tet-On antisense RNA system, flow cytometry, cell viability assay Molecular biology reports Medium 17086444
2010 Overexpression of SURF6 in NIH/3T3 cells stabilized pre-rRNA intragenic transcribed spacers (ITS2 ~7-fold, 5'ETS ~2-fold) without affecting mature rRNA levels, indicating SURF6 prevents premature cleavage of pre-rRNA spacers, analogous to its yeast homologue Rrp14. Dot-hybridization of isolated RNA with biotinylated oligonucleotide probes, Western blot, doxycycline-inducible overexpression system Bioorganicheskaia khimiia Medium 21063453
2014 GST pull-down assay identified SURF6-interacting proteins in HeLa cells including B23/nucleophosmin, nucleolin, EBP2, and UBF (a cofactor of RNA polymerase I), implicating SURF6 in both rDNA transcription and rRNA processing. GST pull-down assay, mass spectrometry Bioorganicheskaia khimiia Medium 25898752
2017 Conditional overexpression of SURF6 in NIH/3T3 cells accelerated cell proliferation, shortened G1 phase by ~30%, and caused accumulation of rRNA species along both ribosomal subunit maturation pathways, establishing SURF6 as a positive regulator of G1/S transition and rRNA processing. Tet-On inducible overexpression, real-time cell proliferation monitoring, flow cytometry, BrdU labeling, Northern blot, qRT-PCR Cell cycle (Georgetown, Tex.) High 28873013
2018 Electrostatically-driven interactions between disordered regions of NPM1 and SURF6 drive liquid-liquid phase separation; heterotypic NPM1-SURF6 and homotypic NPM1-NPM1 scaffolding interactions dynamically interconvert within liquid droplets in response to molecular crowding and protein concentration changes. In vitro phase separation reconstitution, fluorescence microscopy of liquid droplets, quantitative biophysical characterization Nature communications High 30498217
2023 SURF6 knockdown in HeLa and HCT116 cells shifted pre-rRNA processing from pathway 1 to pathway 2, affecting maturation of rRNAs from both small and large ribosomal subunits; SURF6 overexpression had reciprocal effects; cell cycle changes (G0/G1 elongation, G2/M shortening) were p53-independent. siRNA knockdown, overexpression, Northern blot/RT-PCR analysis of rRNA precursors, flow cytometry, p53-deficient cell lines PloS one High 37450438
2024 miR-3655 targets SURF6 to inhibit its transcription; SURF6 in turn inhibits nuclear translocation of IRF7, reducing IRF7-dependent activation of the IFNβ promoter and IFNβ secretion, placing SURF6 in a KRAS-miR3655-SURF6-IRF7-IFNβ signaling axis. miRNA target validation, transcriptomic sequencing, nuclear fractionation, promoter activity assay, loss-of-function experiments Gut microbes Medium 39523457
2025 Super-resolution microscopy revealed SURF6 and rRNA co-localize in a core sub-phase of the nucleolar granular component; in vitro reconstitution showed SURF6/rRNA-rich core and NPM1-rich shell form multiphase condensates; SURF6's association with rRNA is weakened upon ribosomal subunit assembly, enabling NPM1 to extract assembled subunits from condensates, suggesting an assembly-line mechanism for ribosomal subunit efflux. Super-resolution microscopy, in vitro condensate reconstitution, rRNA binding assays, ribosome subunit assembly assays bioRxivpreprint Medium bio_10.1101_2025.03.01.640913

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Compositional adaptability in NPM1-SURF6 scaffolding networks enabled by dynamic switching of phase separation mechanisms. Nature communications 87 30498217
1998 The SURF-6 protein is a component of the nucleolar matrix and has a high binding capacity for nucleic acids in vitro. European journal of cell biology 30 9548374
2006 Implication of nucleolar protein SURF6 in ribosome biogenesis and preimplantation mouse development. Biology of reproduction 27 16855206
1996 The Surf-6 gene of the mouse surfeit locus encodes a novel nucleolar protein. DNA and cell biology 23 8639267
2024 KRAS mutations promote the intratumoral colonization of enterotoxigenic bacteroides fragilis in colorectal cancer through the regulation of the miRNA3655/SURF6/IRF7/IFNβ axis. Gut microbes 18 39523457
2017 Involvement of the specific nucleolar protein SURF6 in regulation of proliferation and ribosome biogenesis in mouse NIH/3T3 fibroblasts. Cell cycle (Georgetown, Tex.) 15 28873013
2005 Identification of an evolutionary conserved SURF-6 domain in a family of nucleolar proteins extending from human to yeast. Biochemical and biophysical research communications 14 15629442
2000 Isolation and genomic analysis of the human surf-6 gene: a member of the Surfeit locus. Gene 11 10675619
2006 The nucleolar protein SURF-6 is essential for viability in mouse NIH/3T3 cells. Molecular biology reports 8 17086444
2023 Human nucleolar protein SURF6/RRP14 participates in early steps of pre-rRNA processing. PloS one 6 37450438
2012 Development of novel mouse hybridomas producing monoclonal antibodies specific to human and mouse nucleolar protein SURF-6. Hybridoma (2005) 5 22316485
2009 Early expression of nucleolar SURF-6 protein in mouse spleen lymphocytes activated for proliferation in vitro. Bulletin of experimental biology and medicine 5 19907743
2005 [Properties and functions of a new nucleolar protein, Surf-6, in 3T3 mouse cells]. Bioorganicheskaia khimiia 5 16363129
2020 A Higher Level of Expression of the Nucleolar Protein SURF6 in Human Normal Activated Lymphocytes and in Lymphocytes of Patients with Lymphoproliferative Disorders. Doklady. Biochemistry and biophysics 3 33119830
2014 [Identification of the protein partners of the human nucleolar protein SURF6 in HeLa cells by GST pull-down assay]. Bioorganicheskaia khimiia 1 25898752
2011 [Cloning, expression, and isolation from Escherichia coli of human protein SURF-6 translationally fused to glutathione S-transferase]. Prikladnaia biokhimiia i mikrobiologiia 1 22808736
2010 [Overexpression of the nucleolar protein SURF-6 in mouse fibroblasts NIH/3T3 leads to stabilisation of intragenic transcribed spacers of the pre-rRNA]. Bioorganicheskaia khimiia 1 21063453
2002 Cloning and expression of the surfeit locus member Surf-6 during embryogenesis in Xenopus laevis. DNA sequence : the journal of DNA sequencing and mapping 1 12391725
2022 Rrp14 controls rRNA transcription via facilitating the translocation of Pol5 into the nucleolus. Cell cycle (Georgetown, Tex.) 0 34974803