UTP23

UTP23 is a conserved, essential nucleolar protein that functions in early small ribosomal subunit (SSU) biogenesis, where it is required for the endonucleolytic cleavage steps that mature 18S rRNA (PMID:16769905, PMID:25190460). It adopts a PIN-domain core fold whose putative active-site residues are catalytically degenerate — single active-site point mutations do not abrogate its function — distinguishing it from the active endonuclease Utp24 (PMID:16769905, PMID:24152547). The structured core is decorated with functional appendages: a CCHC Zn-finger whose cysteine ligands are essential for viability, N-terminal basic helix residues required for RNA binding, and a C-terminal tail that mediates association with the snR30/U17 H/ACA snoRNP and pre-ribosomal incorporation (PMID:24152547). Mechanistically, UTP23 binds RNA tightly but non-specifically on its own and acts in synergy with the snR30 RNP, which provides sequence specificity by base-pairing to expansion segment 6 (ES6) of 18S rRNA while UTP23 enhances overall RNP affinity for the pre-rRNA (PMID:35648701). Cryo-EM shows UTP23 is recruited within a Krr1-UTP23-Kri1 assembly-factor module alongside ribosomal proteins uS11 and uS15 to build an isolated 40S central-domain subdomain prior to its Krr1-dependent integration into the 90S pre-ribosome (PMID:40399280). In activated T cells, DCAF13-driven NPM1 phase separation forms nucleolar condensates that recruit UTP23 to execute 18S rRNA maturation (PMID:37615668). Beyond its canonical nucleolar role, cytoplasmic relocalization of UTP23 in colorectal cancer cells engages KRT5 to promote invasion and metastasis (PMID:38372088).

1. 2006 High

   Established that UTP23 is an essential SSU processome component for early 18S rRNA cleavages and, unexpectedly, that its PIN domain active site is catalytically degenerate rather than a functional nuclease.

   Evidence Yeast depletion strains, nucleolar localization, pre-rRNA processing analysis, and active-site mutagenesis

   PMID:16769905

   Open questions at the time

   • Did not resolve which residues/domains drive function if not catalysis
   • No structural basis for the degenerate active site
2. 2013 High

   Defined the domain architecture underlying UTP23 function by solving the PIN-domain structure and assigning roles to the CCHC Zn-finger (viability), N-terminal basic residues (RNA binding), and C-terminal tail (snR30 interaction and pre-ribosome association).

   Evidence X-ray crystallography of yeast Utp23 PIN domain plus in vivo mutagenesis, in vitro RNA-binding, and co-immunoprecipitation

   PMID:24152547

   Open questions at the time

   • Mechanism by which the Zn-finger contributes to viability unresolved
   • Structure of UTP23 within an intact RNP not determined
3. 2014 Medium

   Extended the rRNA-processing role to mammalian cells, showing UTP23 depletion specifically disrupts ITS1 cleavages required for SSU maturation.

   Evidence siRNA knockdown in mouse cells with RAMP quantitative pre-rRNA profiling

   PMID:25190460

   Open questions at the time

   • Direct enzymatic versus scaffolding contribution not separated
   • Single-lab knockdown without rescue
4. 2022 High

   Resolved how UTP23 achieves specificity by showing it binds RNA non-specifically alone but synergizes with the snR30 RNP, which anchors to ES6 of 18S rRNA, with UTP23 boosting RNP affinity for pre-rRNA.

   Evidence In vitro reconstitution of the yeast snR30 RNP with quantitative EMSA and fluorescence binding assays and deletion/mutation mapping

   PMID:35648701

   Open questions at the time

   • In vitro reconstitution does not capture full 90S context
   • Functional consequence of affinity enhancement on cleavage timing untested
5. 2023 Medium

   Linked UTP23 recruitment to nucleolar phase separation, showing DCAF13-driven NPM1 condensates recruit UTP23 to carry out 18S rRNA maturation during T cell proliferation.

   Evidence Genetic depletion in T cells, phase separation and co-localization imaging, and pre-rRNA processing analysis

   PMID:37615668

   Open questions at the time

   • Whether UTP23 itself is the cleaving endonuclease conflicts with the catalytically degenerate PIN domain evidence
   • Direct UTP23-condensate biophysical interaction not isolated
6. 2024 Low

   Demonstrated a non-canonical, localization-dependent oncogenic role in which cytoplasmic UTP23 binds KRT5 to promote colorectal cancer invasion and metastasis.

   Evidence Subcellular fractionation/immunofluorescence in clinical samples and lines, invasion/migration assays comparing cytoplasmic versus nucleolar UTP23, and mass-spectrometry co-IP

   PMID:38372088

   Open questions at the time

   • Single Co-IP/MS for KRT5 without reciprocal validation
   • Mechanism driving cytoplasmic relocalization unknown
   • Independence from ribosome-biogenesis function not rigorously established
7. 2024 Medium

   Provided evidence that UTP23 is required for survival of a human endocrine cell type, with CRISPR deletion sharply reducing pancreatic beta-cell viability.

   Evidence CRISPR-Cas9 deletion in EndoC-βH3 cells with viability assays

   PMID:38661000

   Open questions at the time

   • Mechanism of lethality (presumed ribosome biogenesis) not directly shown
   • Single method, single lab
8. 2025 High

   Placed UTP23 in a structural assembly pathway, showing it acts within a Krr1-UTP23-Kri1 module with uS11/uS15 to build an isolated 40S central-domain subdomain that is integrated into the 90S after Krr1-dependent snR30 release.

   Evidence Cryo-EM structural analysis with in vivo assembly-factor depletion and pre-rRNA processing assays

   PMID:40399280

   Open questions at the time

   • Temporal coordination between subdomain assembly and cleavage not fully defined
   • UTP23's precise catalytic versus scaffolding role at integration unresolved

• Whether UTP23 contributes any direct catalytic activity to 18S rRNA cleavage, or acts purely as an RNA-binding scaffold/recruitment factor, remains unresolved given its degenerate PIN active site.
• No reconciliation between degenerate active-site evidence and reported endonuclease role
• No reconstituted cleavage assay assigning catalysis to UTP23