Affinage

NOP58

Nucleolar protein 58 · UniProt Q9Y2X3

Length
529 aa
Mass
59.6 kDa
Annotated
2026-06-10
19 papers in source corpus 13 papers cited in narrative 13 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

NOP58 is a core protein of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes that operates in the nucleolus to direct guide-RNA-dependent 2'-O-methylation of pre-rRNA during ribosome biogenesis (PMID:10606270, PMID:41383020). It is a common core component that co-immunoprecipitates with the box C/D family of snoRNAs, and its high-affinity binding to these snoRNAs depends on SUMO modification at K467 and K497 — a regulatory feature that distinguishes it from the related NOP56 (PMID:10606270, PMID:20797632). In complex with fibrillarin, NOP58 (via its archaeal ortholog Nop5) supports SAM-dependent 2'-O-methyltransferase chemistry, and the fibrillarin–Nop5 heterodimer can methylate rRNA even independently of guide RNA (PMID:28576826). Loss of NOP58 reduces fibrillarin levels, depletes box C/D snoRNAs, alters nucleolar morphology, and impairs pre-rRNA maturation, and a hypomorphic splice variant (c.516G>A) that lowers NOP58 to ~12% of normal causes a Mendelian disorder through these pre-rRNA processing defects (PMID:41383020). Selective loading of NOP58 onto the RUVBL1/2 AAA+ ATPase chaperone during snoRNP biogenesis requires the PAQosome cofactor NOPCHAP1, which bridges the CC-NOP domain of NOP58 to RUVBL1/2 domain II in an ATP-sensitive manner and acts as a client-specific factor for NOP58 over NOP56 (PMID:33367824). Beyond canonical ribosome biogenesis, NOP58 is recruited by specific lncRNAs and stabilizes target RNAs: it is guided by lncRNA ZFAS1 to accelerate snoRNP assembly and rRNA methylation (PMID:32443980), regulates SNAIL mRNA stability to drive EMT (PMID:38087130), and interacts with DDX18 to promote DNA damage repair and radioresistance (PMID:41834519).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1999 High

    Established NOP58 as a nucleolar protein physically associated with box C/D snoRNAs, defining it as a core snoRNP component rather than a transient factor.

    Evidence Immunofluorescence and co-immunoprecipitation of snoRNAs from human nuclear extracts

    PMID:10606270

    Open questions at the time
    • Did not resolve which residues mediate snoRNA contact
    • No structural model of the snoRNP at this stage
  2. 2010 High

    Identified SUMOylation at K467/K497 as a post-translational switch required for high-affinity NOP58–snoRNA binding, explaining how snoRNP assembly is regulated and why NOP58 differs from NOP56.

    Evidence SILAC proteomics, in vitro SUMOylation, site-directed mutagenesis, and snoRNA-binding assays

    PMID:20797632

    Open questions at the time
    • SUMO ligase and deconjugase that act on NOP58 not identified
    • Did not establish whether SUMOylation is regulated dynamically during the cell cycle
  3. 2010 Medium

    Mapped the ALFR motif of the archaeal Nop5 Nop domain as a direct contact point with the guide/spacer regions of box C/D RNA, implicating NOP58 in substrate engagement and snoRNP assembly.

    Evidence UV-cross-linking of in vitro assembled Pyrococcus furiosus box C/D sRNP with mutational analysis

    PMID:20962039

    Open questions at the time
    • Archaeal ortholog; human NOP58 contact not directly tested
    • Functional role in substrate release versus binding not resolved
  4. 2017 High

    Demonstrated that the fibrillarin–Nop5 heterodimer carries intrinsic SAM-dependent 2'-O-methyltransferase activity, showing NOP58 can support rRNA methylation chemistry even without guide RNA and L7Ae.

    Evidence In vitro methylation assay with purified Pyrococcus abyssi heterodimer, tritium labeling, MS, and RT mapping

    PMID:28576826

    Open questions at the time
    • Archaeal system; guide-independent activity in human cells not shown
    • Physiological relevance of stand-alone methylation sites unclear
  5. 2019 Medium

    Showed that an assembly factor (Bcd1p) controls co-transcriptional loading of Nop58 onto snoRNA, defining how NOP58 is delivered into nascent snoRNPs.

    Evidence Ordered ChIP, RIP, and protein IP loading assays in yeast

    PMID:30700579

    Open questions at the time
    • Yeast ortholog system
    • Human assembly-factor equivalents not directly tested here
  6. 2020 Medium

    Linked NOP58 to circadian and lncRNA inputs on pre-rRNA processing, broadening its regulation beyond constitutive snoRNP function.

    Evidence BMAL1 interactome by mass spectrometry plus pre-rRNA readouts; ZFAS1 RNA pull-down with rRNA methylation and rescue assays

    PMID:32443980 PMID:32450515

    Open questions at the time
    • Direct versus indirect nature of BMAL1–NOP58 association not fully resolved
    • Mechanism by which lncRNA recruitment is coordinated with canonical snoRNP assembly unclear
  7. 2021 High

    Defined NOPCHAP1 as a client-selective PAQosome cofactor that bridges NOP58 to the RUVBL1/2 chaperone, explaining how NOP58 is specifically chaperoned during snoRNP biogenesis.

    Evidence Co-IP, domain mapping of CC-NOP and RUVBL1/2 domain II, proteomics, and NOPCHAP1 knockout cell lines

    PMID:33367824

    Open questions at the time
    • Structural basis of ATP-driven release not determined
    • How chaperoning hands off to mature snoRNP not resolved
  8. 2023 Medium

    Extended NOP58 function to mRNA stabilization, showing it stabilizes SNAIL mRNA to promote EMT under negative lncRNA control.

    Evidence RIP, RNA pull-down, mRNA half-life assays, and EMT marker Western blots in colorectal cancer cells

    PMID:38087130

    Open questions at the time
    • Sequence/structural determinants of NOP58–mRNA binding undefined
    • Single cancer context; generality of mRNA-stabilizing role untested
  9. 2024 Low

    Associated NOP58 with proliferation and apoptosis control and with circRNA stabilization in cancer models, suggesting non-canonical RNA-stabilizing roles.

    Evidence siRNA/overexpression, colony formation, apoptosis flow cytometry in prostate cancer; dual-luciferase and Actinomycin D stability assays in NSCLC

    PMID:38994624 PMID:39494345

    Open questions at the time
    • Prostate study lacks mechanistic pathway resolution beyond a SUMOylation link
    • circRNA study lacks direct biochemical binding demonstration
    • Effects not independently replicated
  10. 2025 Medium

    Provided causal genetic evidence that NOP58 loss disrupts pre-rRNA maturation in patients, establishing NOP58 as required for normal ribosome biogenesis in humans.

    Evidence Trio exome sequencing, splicing RT-PCR, and Western/RT-qPCR analysis of fibrillarin, snoRNA, and pre-rRNA in patient fibroblasts

    PMID:41383020

    Open questions at the time
    • Single variant/family; full disease spectrum not defined
    • Tissue-specific consequences of partial NOP58 loss not characterized
  11. 2026 Medium

    Identified a direct NOP58–DDX18 interaction that promotes radioresistance by limiting radiation-induced DNA damage, connecting NOP58 to DNA damage repair.

    Evidence Pull-down, siRNA knockdown, γ-H2AX and comet assays, and DDX18 rescue in NSCLC cells

    PMID:41834519

    Open questions at the time
    • Molecular mechanism linking the interaction to repair pathways undefined
    • Single cancer context

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NOP58's canonical snoRNP role mechanistically integrates with its non-canonical mRNA/circRNA stabilization and DNA-repair functions remains unresolved.
  • No structure of human NOP58 in its various RNA-binding modes
  • Whether mRNA/circRNA binding uses the same surfaces as snoRNA binding is unknown
  • How SUMOylation and NOPCHAP1 chaperoning are coordinated in vivo is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0016740 transferase activity 1 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0005730 nucleolus 3
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
BMAL1DDX18FBLNOPCHAP1RUVBL1RUVBL2ZFAS1
Complex memberships
PAQosome (RUVBL1/2 chaperone)box C/D snoRNP

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Human NOP58 (hNop5/Nop58) localizes primarily to the nucleolus and co-immunoprecipitates with the box C/D family of snoRNAs from nuclear extracts, establishing it as a common core component of box C/D snoRNPs. Immunofluorescence localization; co-immunoprecipitation from nuclear extracts RNA (New York, N.Y.) High 10606270
2010 NOP58 is a substrate for SUMO modification at residues K467 and K497, and SUMOylation is essential for high-affinity NOP58 binding to snoRNAs; mutation of these sites reduces snoRNA binding. Unlike NOP58, the closely related NOP56 protein is not a SUMO target. SILAC-based quantitative proteomics to identify SUMOylated nucleolar proteins; in vitro SUMOylation assays; site-directed mutagenesis of K467 and K497; in vivo approaches assessing snoRNA binding Molecular cell High 20797632
2010 In archaeal box C/D sRNPs, the ALFR motif in the Nop domain of Nop5 (archaeal ortholog of NOP58) makes a novel UV-cross-link contact with the guide/spacer regions of the sRNA; both the ALFR motif and the spacer sequence adjacent to box C/C' are required for efficient sRNP assembly in vitro, implicating this interaction in substrate binding and/or release. UV-cross-linking of in vitro assembled Pyrococcus furiosus box C/D sRNP; mutational analysis of ALFR motif and spacer sequences RNA (New York, N.Y.) Medium 20962039
2017 A Pyrococcus abyssi fibrillarin–Nop5 heterodimer performs SAM-dependent 2'-O-methylation of 16S and 23S rRNAs in vitro independently of L7Ae and C/D guide RNAs, identifying at least three novel methylation sites and demonstrating a guide-RNA-independent stand-alone methyltransferase activity of the fibrillarin–Nop5 complex. In vitro 2'-O-methylation assay with purified fibrillarin–Nop5 heterodimer; tritium-labeling; mass spectrometry; reverse transcription mapping of methylation sites RNA (New York, N.Y.) High 28576826
2019 Bcd1p (yeast ortholog of BCD1) acts as an assembly factor for box C/D snoRNP biogenesis by controlling the loading of the core protein Nop58 onto snoRNA; Bcd1p is recruited co-transcriptionally and directs Nop58 loading on immature and mature snoRNA species as demonstrated by ordered chromatin, RNA, and protein immunoprecipitation assays. Chromatin immunoprecipitation; RNA immunoprecipitation; protein immunoprecipitation (ordered loading assays in yeast) RNA (New York, N.Y.) Medium 30700579
2020 BMAL1 localizes to the nucleolus and associates with NOP58 (identified by unbiased mass spectrometry interactome); this interaction is linked to NOP58-associated Snord118 nucleolar levels and cleavage of specific pre-rRNA intermediates, suggesting BMAL1 modulates NOP58-dependent pre-rRNA processing. Biochemical cellular fractionation; immunofluorescence; mass spectrometry interactome (BMAL1 pulldown); northern blot / RT-qPCR for pre-rRNA intermediates iScience Medium 32450515
2020 The lncRNA ZFAS1 recruits NOP58 via specific AAGA/CAGA motifs, which accelerates assembly of SNORD12C/78 snoRNPs and guides 2'-O-methylation at rRNA positions Gm3878 and Gm4593; NOP58 overexpression rescues the anti-proliferative effects of ZFAS1 knockdown, placing NOP58 downstream of ZFAS1 in this axis. RNA pull-down assay; RNA fluorescence in situ hybridization; RTL-P and DPBST assays for rRNA 2'-O-methylation; rescue (overexpression) experiments in vitro and in vivo (xenograft) Molecular cancer Medium 32443980
2021 NOPCHAP1 (C12ORF45) acts as a PAQosome cofactor that bridges NOP58 and the RUVBL1/2 AAA+ ATPases: it makes direct physical interactions with the CC-NOP domain of NOP58 and domain II of RUVBL1/2, and this interaction with RUVBL1/2 is disrupted upon ATP binding. NOPCHAP1 selectively binds NOP58 over the closely related NOP56 and PRPF31, and NOPCHAP1 knockout specifically decreases NOP58 (but not NOP56 or PRPF31) expression, demonstrating client selectivity in snoRNP assembly. NOP58 mutant analysis; co-immunoprecipitation; proteomic experiments; NOPCHAP1 KO cell lines; binding domain mapping Nucleic acids research High 33367824
2023 NOP58 regulates the stability of SNAIL mRNA to promote EMT in colorectal cancer cells; lncRNA CYP1B1-AS1 directly binds NOP58 (validated by RIP and RNA pull-down) and negatively regulates NOP58 to suppress EMT, as confirmed by Western blot of EMT markers and mRNA half-life assays. RNA immunoprecipitation (RIP); RNA pull-down; mRNA half-life (RT-qPCR after transcription inhibition); Western blot of EMT proteins; rescue overexpression experiments Digestive diseases and sciences Medium 38087130
2024 NOP58 knockdown in prostate cancer cells increases BCL2 expression and decreases Ki67 levels, promoting apoptosis and inhibiting proliferation, while NOP58 overexpression promotes colony formation; these effects are linked mechanistically to the SUMOylation pathway. siRNA knockdown and overexpression; colony formation assay; flow cytometry (apoptosis); Western blot (BCL2, Ki67) Frontiers in pharmacology Low 39494345
2024 NOP58 directly binds and stabilizes hsa_circ_0001550 (a circular RNA) in NSCLC cells, as demonstrated by dual-luciferase reporter assay and Actinomycin D stability assay; NOP58 overexpression partially rescues proliferation, migration, invasion, and stemness suppressed by hsa_circ_0001550 knockdown. Dual-luciferase reporter assay; Actinomycin D mRNA/circRNA stability assay; rescue overexpression experiments; EdU, wound healing, transwell, flow cytometry assays Anti-cancer agents in medicinal chemistry Low 38994624
2025 A hypomorphic NOP58 variant (c.516G>A; p.Leu172=) causes exon 7 skipping, reducing NOP58 protein to ~12% of normal levels in patient fibroblasts, concomitantly reducing fibrillarin levels, decreasing box C/D snoRNA accumulation, altering nucleolar morphology, and impairing pre-rRNA maturation (elevated 45S and 21S pre-rRNA, decreased 47S, 32S, and 26S pre-rRNA), establishing that NOP58 is required for normal pre-rRNA processing. Trio whole-exome sequencing; RT-PCR (splicing analysis); Western blot (NOP58, fibrillarin levels); RT-qPCR (snoRNA and pre-rRNA quantification); immunofluorescence (nucleolar morphology) HGG advances Medium 41383020
2026 NOP58 directly interacts with DDX18 (validated by pull-down assay) in NSCLC cells, and this interaction promotes radioresistance by suppressing radiation-induced DNA damage; NOP58 knockdown exacerbates DNA damage (γ-H2AX, comet assay) and apoptosis under irradiation, while DDX18 overexpression reverses these radiosensitizing effects. Pull-down assay (direct protein interaction); siRNA knockdown; γ-H2AX immunofluorescence; comet assay; colony formation; flow cytometry (apoptosis); rescue (DDX18 overexpression) Journal of radiation research Medium 41834519

Source papers

Stage 0 corpus · 19 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Long noncoding RNA ZFAS1 promoting small nucleolar RNA-mediated 2'-O-methylation via NOP58 recruitment in colorectal cancer. Molecular cancer 120 32443980
2010 A proteomic screen for nucleolar SUMO targets shows SUMOylation modulates the function of Nop5/Nop58. Molecular cell 64 20797632
1999 Human Nop5/Nop58 is a component common to the box C/D small nucleolar ribonucleoproteins. RNA (New York, N.Y.) 62 10606270
2019 Long noncoding RNA FAM83A-AS1 facilitates hepatocellular carcinoma progression by binding with NOP58 to enhance the mRNA stability of FAM83A. Bioscience reports 46 31696213
2001 Increased expression of a nucleolar Nop5/Sik family member in metastatic melanoma cells: evidence for its role in nucleolar sizing and function. The American journal of pathology 26 11583964
2020 BMAL1 Associates with NOP58 in the Nucleolus and Contributes to Pre-rRNA Processing. iScience 21 32450515
2021 NOPCHAP1 is a PAQosome cofactor that helps loading NOP58 on RUVBL1/2 during box C/D snoRNP biogenesis. Nucleic acids research 20 33367824
2019 Bcd1p controls RNA loading of the core protein Nop58 during C/D box snoRNP biogenesis. RNA (New York, N.Y.) 20 30700579
2010 A novel Nop5-sRNA interaction that is required for efficient archaeal box C/D sRNP formation. RNA (New York, N.Y.) 13 20962039
2017 Archaeal fibrillarin-Nop5 heterodimer 2'-O-methylates RNA independently of the C/D guide RNP particle. RNA (New York, N.Y.) 7 28576826
2010 The Nop5-L7A-fibrillarin RNP complex and a novel box C/D containing sRNA of Halobacterium salinarum NRC-1. Biochemical and biophysical research communications 7 20206603
2024 The role of NOP58 in prostate cancer progression through SUMOylation regulation and drug response. Frontiers in pharmacology 6 39494345
2017 Nop5 interacts with the archaeal RNA exosome. FEBS letters 6 29159940
2024 Pan-cancer landscape analysis of NOP58 and its oncogenic driving role in lung adenocarcinoma. Scientific reports 5 39528555
2023 NOP58 induction potentiates chemoresistance of colorectal cancer cells through aerobic glycolysis as evidenced by proteomics analysis. Frontiers in pharmacology 4 38149051
2023 CYP1B1-AS1 Delays the Malignant Progression of Colorectal Cancer by Binding with NOP58. Digestive diseases and sciences 3 38087130
2024 Overexpression of NOP58 Facilitates Proliferation, Migration, Invasion, and Stemness of Non-small Cell Lung Cancer by Stabilizing hsa_circ_0001550. Anti-cancer agents in medicinal chemistry 2 38994624
2026 NOP58 modulates radiosensitivity in non-small cell lung cancer via DDX18-mediated DNA damage repair. Journal of radiation research 0 41834519
2025 A homozygous synonymous NOP58 variant causes a neurodevelopmental disorder by impairing maturation of pre-ribosomal RNAs. HGG advances 0 41383020

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