Surfeit locus protein 6 · UniProt O75683
SURF6 is a highly basic nucleolar matrix protein that binds nucleic acids with preference for RNA and functions in pre-rRNA processing during ribosome biogenesis (PMID:9548374, PMID:37450438). It localizes to the granular component of the nucleolus, the site of late ribosome maturation, and is retained in residual nucleoli after removal of soluble and chromatin-associated proteins, marking it as a structural matrix constituent (PMID:8639267, PMID:9548374). SURF6 co-localizes with B23/nucleophosmin (NPM1) and fibrillarin and physically associates with a set of nucleolar processing factors including NPM1, nucleolin, EBP2, and an RNA polymerase I cofactor, with the conserved C-terminal domain sufficient for these interactions (PMID:9548374, PMID:25898752). Functionally, SURF6 acts in early pre-rRNA processing steps for both small and large ribosomal subunits and stabilizes intragenic transcribed spacers of pre-rRNA (ITS2, 5'ETS), with its perturbation shifting rRNA biogenesis between alternative processing pathways (PMID:21063453, PMID:37450438). SURF6 is essential for mammalian cell viability and for G1/S cell cycle progression: depletion causes G1 arrest and cell death and reduces rRNA accumulation, whereas overexpression accelerates proliferation and rRNA synthesis, and these cell cycle effects are p53-independent (PMID:17086444, PMID:28873013, PMID:37450438). Mechanistically, electrostatically driven interactions between the disordered regions of NPM1 and SURF6 drive liquid-liquid phase separation, generating multiphase condensates with a SURF6/rRNA-rich core and an NPM1-rich shell in which weakening of SURF6-rRNA association upon subunit assembly permits NPM1-mediated efflux of assembled subunits from the granular component [PMID:30498217, PMID:bio_10.1101_2025.03.01.640913]. A distinct non-canonical activity in colorectal cancer, in which SURF6 suppresses IRF7 nuclear translocation to dampen IFNβ signaling, has been described (PMID:39523457).
Established where SURF6 acts by placing it in the nucleolar granular component, the compartment associated with ribosome maturation.
Evidence Immunofluorescence and immunoblot localization in mammalian cells
Defined SURF6 as a structural nucleolar matrix protein with a biochemical preference for RNA, framing it as a candidate scaffold/RNA-binding factor rather than a soluble enzyme.
Evidence Nuclear matrix fractionation, in vitro nucleic acid binding with recombinant and endogenous protein, and co-immunolabeling with B23/nucleophosmin and fibrillarin
Dissected the determinants of nucleolar targeting, showing multiple regions suffice and that targeting does not require the conserved C-terminal domain, and confirmed in-situ RNA (not DNA) association in interphase nucleoli.
Evidence GFP-fusion deletion analysis and in situ RNase/DNase treatment with immunofluorescence in mouse cells
Demonstrated that SURF6 is functionally required for ribosome biogenesis and viability, linking its loss to reduced 18S rRNA, developmental arrest, and G1 arrest with cell death.
Evidence RNAi in mouse preimplantation embryos and conditional antisense depletion in NIH/3T3 cells with rRNA quantification and flow cytometry
Provided a mechanistic readout for SURF6 in processing by showing it stabilizes pre-rRNA intragenic spacers (ITS2, 5'ETS) without altering mature rRNA, implying protection against premature spacer cleavage.
Evidence Inducible overexpression in NIH/3T3 cells with dot hybridization against pre-rRNA regions
Identified SURF6's direct protein partners, anchoring it within a nucleolar processing network and mapping the binding activity to the conserved C-terminal domain.
Evidence GST pull-down with mass spectrometry from HeLa extracts
Showed SURF6 abundance is rate-limiting for proliferation and ribosome production, with overexpression shortening cell cycle phases and increasing rRNA along both subunit maturation pathways.
Evidence Tet-On overexpression with proliferation monitoring, flow cytometry, BrdU labeling, Northern blot and qRT-PCR
Revealed the biophysical basis of SURF6 function by showing its disordered region drives electrostatic liquid-liquid phase separation with NPM1, with heterotypic and homotypic scaffolding interactions interconverting under crowding.
Evidence In vitro reconstitution with purified proteins and fluorescence microscopy of droplets
Established that human SURF6 acts in early pre-rRNA processing for both subunits, biases pathway choice, and exerts p53-independent cell cycle control.
Evidence Bidirectional siRNA knockdown and overexpression in HeLa and isogenic p53+/+ and p53-/- HCT116 cells with rRNA precursor and flow cytometry readouts
Described a non-canonical SURF6 activity in colorectal cancer, suppressing IRF7 nuclear translocation and IFNβ promoter activation, with miR3655 controlling SURF6 levels.
Evidence miR3655 modulation, SURF6 perturbation, transcriptomics, IFNβ reporter assays, and IRF7 nuclear fractionation in colorectal cancer context
Integrated SURF6, NPM1, and rRNA into a multiphase condensate model in which SURF6-rRNA affinity loss upon subunit assembly enables NPM1-driven efflux, proposing an assembly-line mechanism for the granular component.
Evidence Super-resolution microscopy and in vitro reconstitution of multiphase condensates with purified components (preprint)
PMID:bio_10.1101_2025.03.01.640913
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 1996 | SURF6 protein is localized in the nucleolus, specifically in the nucleolar granular component, a structure involved in ribosome maturation. | Immunofluorescence and immunoblot analyses | DNA and cell biology | Medium | 8639267 |
| 1998 | SURF6 is a component of the nucleolar matrix and binds both DNA and RNA in vitro, with preferential binding to RNA. It is retained in residual nucleoli after depletion of soluble and chromatin-related proteins. | Immunofluorescence on nuclear matrix preparations, immunoblot of nucleolar subfractions, in vitro nucleic acid binding assays with endogenous and recombinant SURF6 | European journal of cell biology | High | 9548374 |
| 1998 | SURF6 co-localizes with nucleolar proteins B23/nucleophosmin and fibrillarin in interphase and mitosis, appearing in the perichromosomal layer, cytoplasm, and prenucleolar bodies during mitosis, but its dynamics differ partially from both markers. | Double immunolabeling/immunofluorescence in interphase and mitotic cells | European journal of cell biology | Medium | 9548374 |
| 2005 | Multiple regions of SURF6 are capable of nucleolar targeting independently of the evolutionary conserved C-terminal SURF6 domain, as shown by deletion analysis with GFP fusion proteins. | GFP fusion protein expression and deletion sequence analysis in mammalian cells | Biochemical and biophysical research communications | Medium | 15629442 |
| 2005 | In interphase nucleoli of mouse 3T3 cells, SURF6 is associated with RNA but not DNA in situ. During mitosis, SURF6 appears in forming nucleoli after fibrillarin and B23/nucleophosmin, suggesting involvement in terminal stages of ribosomal particle assembly. | In situ RNase A and DNase I treatment with immunofluorescence; temporal analysis of nucleolar protein appearance in telophase | Bioorganicheskaia khimiia | Medium | 16363129 |
| 2006 | Knockdown of Surf6 mRNA by RNAi in mouse preimplantation embryos led to developmental arrest at the 8-cell/morula stage and a decrease in 18S rRNA levels, indicating SURF6 is essential for ribosome biogenesis during early development. | RNAi knockdown in mouse preimplantation embryos; immunocytochemistry; rRNA quantification | Biology of reproduction | Medium | 16855206 |
| 2006 | Conditional antisense RNA-mediated depletion of SURF6 in mouse NIH/3T3 cells caused cell death and apparent G1 phase arrest, establishing SURF6 as essential for mammalian cell viability and cell cycle progression. | Tet-On regulated antisense RNA expression; flow cytometry for cell cycle analysis | Molecular biology reports | Medium | 17086444 |
| 2010 | Overexpression of SURF6 in mouse NIH/3T3 fibroblasts stabilizes intragenic transcribed spacers of pre-rRNA (ITS2 ~7-fold, 5'ETS ~2-fold) without changing mature rRNA levels, suggesting SURF6 prevents premature cleavage of pre-rRNA spacers during processing. | Doxycycline-inducible overexpression; dot hybridization of RNA with oligonucleotide probes to pre-rRNA regions | Bioorganicheskaia khimiia | Medium | 21063453 |
| 2014 | Human SURF6 (GST-SURF6 fusion) interacts by pulldown with key nucleolar RNA processing factors including B23/nucleophosmin, nucleolin, EBP2, and a cofactor of RNA polymerase I (UBE) in HeLa cell extracts. The conserved C-terminal domain alone is sufficient for these interactions. | GST pull-down assay followed by mass spectrometry identification | Bioorganicheskaia khimiia | Medium | 25898752 |
| 2017 | Conditional overexpression of SURF6 in mouse NIH/3T3 fibroblasts accelerates cell proliferation, reduces population doubling time (~19.8 to ~16.2 h), shortens all cell cycle phases (especially G1 by ~30%), and increases accumulation of rRNA species along both ribosomal subunit maturation pathways. | Tet-On inducible overexpression; real-time cell proliferation monitoring; flow cytometry; BrdU labeling; Northern blots and qRT-PCR | Cell cycle (Georgetown, Tex.) | High | 28873013 |
| 2018 | Electrostatically driven interactions between disordered regions of NPM1 and SURF6 drive liquid-liquid phase separation. Within NPM1-SURF6 liquid-phase droplets, heterotypic (NPM1-SURF6) and homotypic (NPM1-NPM1) scaffolding interactions dynamically interconvert in response to changes in molecular crowding and protein concentrations. | In vitro reconstitution of phase separation with purified proteins; fluorescence microscopy of liquid droplets; quantitative analysis of droplet composition under varying concentrations | Nature communications | High | 30498217 |
| 2023 | Human SURF6 knockdown and overexpression in HeLa and HCT116 cells demonstrate that SURF6 participates in maturation of rRNAs from both small and large ribosomal subunits (early pre-rRNA processing steps). SURF6 knockdown shifts rRNA biogenesis from pathway 1 to pathway 2. Cell cycle effects (elongated G0/G1, shortened G2/M) upon SURF6 knockdown are p53-independent. | siRNA knockdown and overexpression in HeLa and HCT116 (p53+/+ and p53-/-) cells; analysis of rRNA precursor abundance; flow cytometry for cell cycle analysis | PloS one | High | 37450438 |
| 2024 | SURF6 promotes intratumoral colonization of ETBF in colorectal cancer by inhibiting nuclear translocation of IRF7, thereby suppressing IFNβ promoter activation. miR3655 targets SURF6 to inhibit its transcription and is required for this regulatory axis. | miR3655 modulation, SURF6 knockdown/overexpression, transcriptomic sequencing, reporter assays for IFNβ promoter, nuclear fractionation for IRF7 localization | Gut microbes | Medium | 39523457 |
| 2025 | In vitro reconstitution showed that NPM1, SURF6, and rRNA form multiphase condensates with a SURF6/rRNA-rich core and NPM1-rich shell. SURF6's association with rRNA is weakened upon ribosome subunit assembly, enabling NPM1 to extract assembled subunits from condensates, suggesting an assembly-line mechanism for subunit efflux from the granular component. | Super-resolution microscopy; in vitro reconstitution of multiphase condensates with purified components; functional perturbation of condensate composition | bioRxivpreprint | Medium | bio_10.1101_2025.03.01.640913 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2018 | Compositional adaptability in NPM1-SURF6 scaffolding networks enabled by dynamic switching of phase separation mechanisms. | Nature communications | 89 | 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 | 24 | 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 | 22 | 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 | 15 | 15629442 |
| 2000 | Isolation and genomic analysis of the human surf-6 gene: a member of the Surfeit locus. | Gene | 12 | 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 |
| 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 | 2 | 12391725 |
| 2022 | Rrp14 controls rRNA transcription via facilitating the translocation of Pol5 into the nucleolus. | Cell cycle (Georgetown, Tex.) | 1 | 34974803 |
| 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 |
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