Affinage

UTP18

U3 small nucleolar RNA-associated protein 18 homolog · UniProt Q9Y5J1

Length
556 aa
Mass
62.0 kDa
Annotated
2026-06-11
12 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UTP18 is a WD-repeat assembly factor of ribosome biogenesis that operates as a core structural and adaptor component of the small-subunit (SSU) processome/90S preribosome required for 18S rRNA maturation (PMID:15590835, PMID:28967883). It is a stable subunit of the Pwp2-containing UtpB subcomplex, where its N-terminal region is contacted directly by Utp6 to fix its architectural position, and this subcomplex engages the 5' end of the 35S pre-rRNA to drive initial 90S assembly steps independently of the U3 snoRNP (PMID:15231838, PMID:18725399). Beyond its scaffolding role, UTP18 carries an arch-interacting motif (AIM) through which it docks onto the KOW domain of the RNA helicase Mtr4; structural and NMR analysis show the KOW domain simultaneously binds the AIM and structured RNA, allowing UTP18 to recruit the Mtr4-associated nuclear exosome onto cleaved pre-rRNA fragments for degradation (PMID:26317469, PMID:28883156). In human cells, UTP18 resides predominantly in the nucleolar dense fibrillar and granular components but redistributes to cap and body regions upon transcription arrest (PMID:24754225); a subset is exported to the cytoplasm, where, in association with Hsp90 and the translation machinery, it upregulates cap-independent (IRES-mediated) translation of HIF1α, Myc, and VEGF to promote stress resistance (PMID:25435373). This nucleocytoplasmic shuttling is governed by deSUMOylation, and cytoplasmic UTP18 destabilizes p21 mRNA to drive cell-cycle progression and tumorigenesis in colorectal cancer (PMID:37086406).

Mechanistic history

Synthesis pass · year-by-year structured walk · 7 steps
  1. 2004 Medium

    Established that UTP18 is a genuine ribosome biogenesis factor rather than an uncharacterized WD-repeat protein, placing it within the machinery that generates 18S rRNA.

    Evidence Co-immunoprecipitation with SSU processome markers Mpp10, U3 snoRNA, and pre-rRNAs; reciprocal co-IP and gradient sedimentation defining a Pwp2-containing subcomplex contacting the 5' end of 35S pre-rRNA

    PMID:15231838 PMID:15590835

    Open questions at the time
    • Catalytic or structural contribution within the processome not resolved
    • Did not define direct binding partners at residue level
  2. 2008 Medium

    Resolved where UTP18 sits architecturally by mapping a direct Utp6-UTP18 contact, defining its position within the UtpB subcomplex.

    Evidence Co-immunoprecipitation and interaction mapping with deletion mutants plus biophysical methods

    PMID:18725399

    Open questions at the time
    • Functional consequence of the Utp6 contact for assembly not directly tested
    • Full UtpB topology not established by this work alone
  3. 2014 Medium

    Revealed a second, non-ribosomal function: cytoplasmic UTP18 promotes cap-independent translation of stress transcripts, expanding its role beyond the nucleolus.

    Evidence GFP live-cell imaging, FRAP, fractionation, co-IP with translation machinery and Hsp90, and IRES reporter translation assays under serum withdrawal; separate imaging/FRAP showing nucleolar relocalization upon transcription arrest

    PMID:24754225 PMID:25435373

    Open questions at the time
    • Mechanism by which UTP18 stimulates IRES translation not defined
    • Signal triggering cytoplasmic export not identified in this work
  4. 2015 High

    Defined the molecular basis for UTP18's role in rRNA surveillance, showing it acts as an adaptor that recruits Mtr4/exosome to substrate RNA via a defined motif.

    Evidence Biochemical adaptor identification, reciprocal interaction mapping, and AIM consensus motif identification docking to the Mtr4 KOW domain

    PMID:26317469

    Open questions at the time
    • Atomic details of the AIM-KOW contact not yet resolved at this stage
    • In vivo kinetics of exosome recruitment not measured
  5. 2017 High

    Provided atomic-level mechanism for both the assembly and adaptor roles, fixing UTP18 within the 90S network and showing how the KOW domain binds AIM and RNA simultaneously.

    Evidence 3.2 Å cryo-EM of the 90S preribosome with atomic model; 3.2 Å crystal structure of Mtr4 bound to an AIM peptide plus NMR mapping of simultaneous AIM/RNA binding

    PMID:28883156 PMID:28967883

    Open questions at the time
    • AIM structure solved for Nop53 analogue rather than UTP18 itself
    • Dynamics of exosome handoff during processing not captured by static structures
  6. 2023 Medium

    Connected UTP18 localization control to disease, showing deSUMOylation drives cytoplasmic translocation where UTP18 destabilizes p21 mRNA to promote tumorigenesis.

    Evidence Quantitative proteomics, SUMOylation/deSUMOylation assays, mRNA stability assays, and organoid overexpression in colorectal cancer

    PMID:37086406

    Open questions at the time
    • Direct mechanism of p21 mRNA destabilization (RNA binding vs. indirect) not established
    • SUMO sites and responsible enzymes not fully mapped
  7. 2025 Low

    Refined the spatial context of UTP18-mediated surveillance, placing the exosome, Mtr4, and Nop53 with Utp18 in the nucleolar granular component.

    Evidence Fluorescence microscopy and subnucleolar localization comparison in yeast

    PMID:40266794

    Open questions at the time
    • Utp18 role inferred from co-localization without direct functional validation in this study
    • Causal contribution of granular-component positioning to exosome access untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How UTP18 is partitioned between its nucleolar biogenesis/surveillance roles and its cytoplasmic translation-regulatory role, and whether the same molecular surfaces are used, remains unresolved.
  • No structural basis for cytoplasmic UTP18-Hsp90/translation machinery interaction
  • Unclear whether cytoplasmic functions require the AIM or WD-repeat surfaces used in the nucleolus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 2 GO:0003723 RNA binding 1 GO:0045182 translation regulator activity 1
Localization
GO:0005730 nucleolus 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
DIP2HSP90MPP10MTR4PWP2UTP13UTP21UTP6
Complex memberships
SSU processome / 90S preribosomeUtpB subcomplex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2015 Utp18 acts as an adaptor protein that recruits the exosome-associated helicase Mtr4 to cleaved rRNA fragments destined for degradation by the exosome. Utp18 contains an arch-interacting motif (AIM) through which it docks to the 'arch' (KOW) domain of Mtr4, targeting it to specific RNA substrates. Biochemical identification of adaptor proteins, interaction mapping, consensus motif identification Cell High 26317469
2017 Atomic structure of the 90S preribosome at 3.2 Å resolution revealed the structural position of Utp18 within the assembly, showing how it is integrated into the highly intertwined network of assembly factors that guide pre-rRNA folding during 40S biogenesis. Cryo-EM structure determination at 3.2 Å resolution with atomic model building Nature structural & molecular biology High 28967883
2017 Crystal structure of Mtr4 bound to the AIM-containing region of Nop53 (an analogue of Utp18) at 3.2 Å revealed that the KOW domain of Mtr4 recognizes the AIM sequence via hydrophobic and electrostatic interactions. NMR showed the KOW domain can simultaneously bind an AIM-containing protein and structured RNA at adjacent surfaces, explaining how Utp18/Nop53 adaptors dock the exosome onto RNPs. X-ray crystallography (3.2 Å), NMR spectroscopy RNA (New York, N.Y.) High 28883156
2004 Utp18 is a bona fide component of the SSU processome (small-subunit processome) required for 18S rRNA biogenesis, confirmed by co-immunoprecipitation with Mpp10, U3 snoRNA, and pre-rRNAs. Co-immunoprecipitation with SSU processome markers (Mpp10, U3 snoRNA, pre-rRNAs) Eukaryotic cell Medium 15590835
2004 Utp18 is part of a stable subcomplex with Pwp2, Dip2, Utp6, Utp13, and Utp21 within the 90S pre-ribosome. This Pwp2-containing subcomplex directly interacts with the 5' end of the 35S pre-rRNA and is essential for initial assembly steps of the 90S pre-ribosome, functioning independently of the U3 snoRNP. Immunoprecipitation, gradient sedimentation analysis, pre-rRNA interaction assay The Journal of biological chemistry Medium 15231838
2008 Utp18 is a component of the UtpB subcomplex of the SSU processome, and the N-terminal domain of Utp6 directly interacts with Utp18, placing Utp18 in a defined architectural position within UtpB. Co-immunoprecipitation, interaction mapping with deletion mutants, biophysical methods Molecular and cellular biology Medium 18725399
2014 Human UTP18 localizes predominantly to the nucleolus (dense fibrillar component and granular component), but a subset localizes to the cytoplasm. Serum withdrawal increases cytoplasmic UTP18 localization. In the cytoplasm, UTP18 associates with the translation complex and Hsp90 to upregulate translation of IRES-containing transcripts (HIF1α, Myc, VEGF), promoting stress resistance. Hsp90 inhibition decreases cytoplasmic UTP18 and UTP18-induced translation increases. GFP live-cell imaging, FRAP, cellular fractionation, co-immunoprecipitation with translation complex and Hsp90, translation assays with IRES reporters Oncogene Medium 25435373
2014 In human HeLa cells, GFP-UTP18 (a UTP-B subcomplex component) localizes to the dense fibrillar component and granular component of nucleoli; when rRNA transcription is suppressed, the majority relocates to cap and body regions of nucleoli. Half of GFP-UTP18 shows low mobility by FRAP, consistent with tight association with macromolecular complexes acting as nucleolar scaffold. Live-cell GFP fluorescence imaging, FRAP, rRNA transcription inhibition Biochemistry and cell biology Medium 24754225
2023 deSUMOylation of UTP18 induces its nucleocytoplasmic transport; once in the cytoplasm, UTP18 mediates instability of p21 mRNA, thereby driving cell-cycle progression and tumorigenesis in colorectal cancer. Quantitative proteomics, SUMOylation/deSUMOylation assays, mRNA stability assays, organoid overexpression experiments Cell reports Medium 37086406
2025 Within the yeast nucleolus, the exosome co-localizes with Mtr4 and Nop53 in the granular component, and Utp18 functions as an Mtr4-dependent adaptor facilitating exosome access to pre-ribosomal particles at this location. Fluorescence microscopy, subnucleolar localization comparison Molecular biology of the cell Low 40266794

Source papers

Stage 0 corpus · 12 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 The Exosome Is Recruited to RNA Substrates through Specific Adaptor Proteins. Cell 169 26317469
2004 The small-subunit processome is a ribosome assembly intermediate. Eukaryotic cell 142 15590835
2017 3.2-Å-resolution structure of the 90S preribosome before A1 pre-rRNA cleavage. Nature structural & molecular biology 90 28967883
2004 Functional characterization of Pwp2, a WD family protein essential for the assembly of the 90 S pre-ribosomal particle. The Journal of biological chemistry 75 15231838
2008 A direct interaction between the Utp6 half-a-tetratricopeptide repeat domain and a specific peptide in Utp21 is essential for efficient pre-rRNA processing. Molecular and cellular biology 42 18725399
2017 Structural insights into the interaction of the nuclear exosome helicase Mtr4 with the preribosomal protein Nop53. RNA (New York, N.Y.) 37 28883156
2014 Dynamics of WD-repeat containing proteins in SSU processome components. Biochemistry and cell biology = Biochimie et biologie cellulaire 17 24754225
2023 UTP18-mediated p21 mRNA instability drives adenoma-carcinoma progression in colorectal cancer. Cell reports 10 37086406
2014 A small subunit processome protein promotes cancer by altering translation. Oncogene 10 25435373
2015 Genome-wide screening of Saccharomyces cerevisiae genes regulated by vanillin. Journal of microbiology and biotechnology 5 25269814
2018 Genome-wide evidences of bisphenol a toxicity using Schizosaccharomyces pombe. Archives of pharmacal research 4 30099677
2025 New insights into nuclear import and nucleolar localization of yeast RNA exosome subunits. Molecular biology of the cell 1 40266794

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