Affinage

PDCD11

Protein RRP5 homolog · UniProt Q14690

Length
1871 aa
Mass
208.7 kDa
Annotated
2026-06-10
21 papers in source corpus 14 papers cited in narrative 14 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/5 claims corpus-supported (80%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDCD11 (the human homolog of yeast Rrp5) is a large multi-domain RNA-binding protein and a central coordinator of nucleolar ribosome biogenesis, uniquely required for both 18S rRNA maturation and 5.8S/28S rRNA synthesis (PMID:8896463, PMID:17654514). Acting through 12 tandem S1 RNA-binding domains, it binds pre-rRNA at multiple sites: its C-terminal domain crosslinks to sequences flanking cleavage site A2 and to the U3, U14, snR30, and snR10 snoRNAs that direct A0–A2 cleavage, while its N-terminal domain binds near site A3 and the RNase MRP RNA component required for 5.8S/28S synthesis (PMID:21233221, PMID:24239293). In humans it associates with the U3 snoRNP within an early 50S SSU processome intermediate before later subcomplexes join (PMID:17654514, PMID:19332556). Mechanistically, Rrp5/PDCD11 functions as a checkpoint coupling the 40S and 60S assembly pathways: early in transcription it blocks Rcl1 access to nascent rRNA, and binding of the 60S factors Noc1/Noc2 to domain I of 25S rRNA alters its RNA-binding mode to license pre-40S cleavage, while ATP hydrolysis by the DEAD-box helicase Rok1 drives its release from pre-40S particles so it can join 60S assembly (PMID:27280440, PMID:31217256). Beyond the nucleolus, extra-nucleolar PDCD11 in p53-mutant cancer cells binds the C-MYC transactivation domain to block SKP2-mediated ubiquitination, stabilizing C-MYC and promoting proliferation and metastasis (PMID:40051297), and in zebrafish it directs microglia differentiation by differentially regulating the NF-κB subunits P65 and c-Rel (PMID:32709934).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Established that a single factor could be simultaneously required for the two divergent cleavage pathways of ribosome biogenesis, defining Rrp5 as a candidate coordinator linking 18S and 5.8S/28S synthesis.

    Evidence Genetic depletion of Rrp5p in S. cerevisiae with pre-rRNA processing analysis and a synthetic-lethality screen with snR10

    PMID:8896463

    Open questions at the time
    • Molecular basis of dual-site requirement not resolved
    • Domain architecture responsible for each cleavage not mapped
  2. 2002 Medium

    Connected snR10 function to Rrp5 genetically, refining how snoRNA partners contribute to Rrp5-dependent processing efficiency rather than the A2 cleavage step itself.

    Evidence Multicopy suppressor screen with Northern and polysome readouts in yeast

    PMID:12242501

    Open questions at the time
    • Suppression did not restore A2 cleavage, leaving the mechanism of rate improvement unclear
    • Physical Rrp5–snR10 contact not demonstrated here
  3. 2008 High

    Extended Rrp5 function to humans, showing PDCD11/NFBP is a nucleolar U3 snoRNA-associated factor required for 18S maturation, conserving the yeast role.

    Evidence Co-IP, immunofluorescence colocalization, and Northern analysis of pre-rRNA upon NFBP knockdown in human cells

    PMID:17654514

    Open questions at the time
    • Direct vs indirect U3 association not distinguished
    • Role in 5.8S/28S synthesis in human cells not tested here
  4. 2009 Medium

    Placed human PDCD11 within a defined early assembly intermediate, showing it joins the U3 snoRNP and a 50S SSU processome before later subcomplexes assemble.

    Evidence Sucrose gradient sedimentation and co-IP with tUTP depletion in human cells

    PMID:19332556

    Open questions at the time
    • Recruitment order inferred, not directly ordered
    • Single lab, complex membership not reconstituted
  5. 2011 High

    Resolved how the 12 tandem S1 domains partition labor, showing the first nine provide high-affinity non-specific binding and the last three confer pre-rRNA specificity, and that separable N/C fragments together support viability.

    Evidence In vitro RNA binding, DMS probing, truncation affinity measurements, and yeast complementation

    PMID:21233221

    Open questions at the time
    • Structural basis of S1 specificity not solved here
    • How the two fragments coordinate in vivo unclear
  6. 2013 High

    Mapped Rrp5's two domains to distinct functional sites in vivo, explaining its dual role: the CTD contacts site A2 and A0–A2 snoRNAs while the NTD contacts site A3 and the RNase MRP RNA.

    Evidence In vivo UV crosslinking with nucleotide resolution, intramolecular complementation, and chromatin-spread EM

    PMID:24239293

    Open questions at the time
    • Direct vs bridged contacts with snoRNAs/MRP RNA not fully separated
    • How compaction defect arises mechanistically not detailed
  7. 2016 High

    Identified the ATPase switch governing Rrp5 dynamics, showing Rok1 ATP hydrolysis releases Rrp5 from pre-40S particles to enable its 60S role.

    Evidence In vitro ATP/ADP-bound Rok1 binding assays, co-IP, and yeast genetics with inactivation mutants

    PMID:27280440

    Open questions at the time
    • Structural detail of the Rok1–Rrp5 interface not resolved
    • How Has1 interaction contributes mechanistically unclear
  8. 2018 High

    Provided structural and biochemical dissection of the C-terminal region, showing the TPR module lacks RNA binding while preceding S1 domains bind RNA.

    Evidence X-ray crystallography (PDB 5NLG) and in vitro RNA binding with domain-deletion constructs

    PMID:30338212

    Open questions at the time
    • Functional role of the TPR module not defined
    • Full-length structure on pre-ribosome not determined
  9. 2019 High

    Defined Rrp5 as a transcription-coupled checkpoint that couples the two subunit pathways, blocking Rcl1 access until Noc1/Noc2 binding of 25S domain I licenses pre-40S cleavage.

    Evidence Quantitative RNA binding and cleavage assays plus genetic epistasis (Noc1 mutants rescued by Rcl1 overexpression) and in vivo co-IP

    PMID:31217256

    Open questions at the time
    • Conservation of this checkpoint logic in humans not shown
    • Structural transition of Rrp5 RNA-binding mode not visualized
  10. 2022 Medium

    Linked helicase activity to subnucleolar positioning, showing Rok1 is required for accurate intranucleolar localization of Rrp5 and for ITS1/ITS2 processing in Drosophila.

    Evidence rok1 mutant genetics, FISH for ITS1/ITS2, and immunofluorescence localization

    PMID:35628496

    Open questions at the time
    • Direct cause of mislocalization not established
    • Relationship to the yeast release mechanism not connected experimentally
  11. 2005 Medium

    Revealed an early non-ribosomal activity, with NFBP/PDCD11 binding HIV-1 Tat and modulating LTR transcription, hinting at extra-nucleolar regulatory roles.

    Evidence Co-IP, colocalization, Tat domain mapping, and LTR reporter assays in human cells

    PMID:15887232

    Open questions at the time
    • Physiological relevance to viral replication not established
    • Mechanism of differential LTR effects unclear
  12. 2020 Medium

    Demonstrated an organismal developmental role beyond ribosome biogenesis, with PDCD11 directing microglia differentiation through differential NF-κB subunit regulation.

    Evidence Zebrafish pdcd11 loss-of-function with immunofluorescence and cytokine/transcriptional readouts

    PMID:32709934

    Open questions at the time
    • Direct molecular target linking PDCD11 to P65 vs c-Rel not identified
    • Conservation in mammalian microglia not tested
  13. 2025 Medium

    Defined a pro-oncogenic moonlighting function, with extra-nucleolar PDCD11 stabilizing C-MYC by shielding it from SKP2-mediated ubiquitination in p53-mutant cancers.

    Evidence Co-IP, C-MYC TAD domain mapping, ubiquitination assays, knockdown stability readouts, and xenograft tumor models

    PMID:40051297

    Open questions at the time
    • How nucleolar vs nucleoplasmic PDCD11 partitioning is regulated unclear
    • Dependence on p53 status mechanistically undefined
  14. 2025 Low

    Implicated PDCD11 in viral packaging into extracellular vesicles and a putative nuclear MRPL2 interaction affecting calcium signaling.

    Evidence ASO depletion with qRT-PCR for HBV RNAs in EVs, LC-MS/MS proteomics, and interaction network/localization analysis

    PMID:41425093

    Open questions at the time
    • MRPL2–PDCD11 interaction based on colocalization/network analysis without direct binding validation
    • Mechanism of HBV RNA loading into EVs not established
    • Not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the conserved ribosome-assembly machine is repurposed for extra-nucleolar functions, and what governs PDCD11's partitioning between the nucleolus and nucleoplasm, remains open.
  • No structural model of full-length human PDCD11 on a pre-ribosome
  • Regulatory cues directing PDCD11 to non-ribosomal substrates (C-MYC, NF-κB) unknown
  • Human relevance of yeast Noc1/Noc2/Rok1 checkpoint not directly tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4
Localization
GO:0005730 nucleolus 3 GO:0005654 nucleoplasm 1
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-1852241 Organelle biogenesis and maintenance 2
Complex memberships
RNase MRP (RNA association)SSU processome / U3 snoRNP

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 RRP5 (yeast ortholog of PDCD11) is essential for pre-rRNA processing at sites A0, A1, and A2 (required for 18S rRNA synthesis) and at site A3 (required for the major short form of 5.8S rRNA synthesis), making it the first cellular component simultaneously required for both snoRNP-dependent and RNase MRP-dependent cleavage events in ribosome biogenesis. Genetic depletion of Rrp5p in S. cerevisiae followed by pre-rRNA processing analysis; synthetic lethality screen with snR10 deletion The EMBO journal High 8896463
2008 Human NFBP (PDCD11) colocalizes with and co-precipitates U3 snoRNA in the nucleolus, and is essential for 18S rRNA maturation via cleavages at sites A0, 1, and 2, as demonstrated by accumulation of unprocessed rRNA intermediates upon NFBP knockdown. Co-immunoprecipitation, immunofluorescence colocalization, Northern blot analysis of pre-rRNA processing upon NFBP depletion Journal of cellular physiology High 17654514
2009 Human RRP5 (PDCD11) associates with the U3 snoRNP as part of a 50S SSU processome assembly intermediate, together with nucleolin and DBP4, and is likely recruited to pre-rRNA through RNA-binding activity to form this intermediate before tUTP, bUTP, MPP10 and BMS1/RCL1 subcomplexes join. Sucrose gradient sedimentation, co-immunoprecipitation, depletion of tUTP proteins to accumulate intermediate complex Molecular and cellular biology Medium 19332556
2011 Yeast Rrp5 binds pre-rRNA at three distinct regions within ITS1 using its 12 tandem S1 RNA-binding domains; the first nine S1 motifs contribute high-affinity but non-specific RNA binding, while the last three S1 domains provide specificity for pre-rRNA. Two truncated forms (Rrp5N and Rrp5C) together fully restore growth in vivo. In vitro RNA binding assays, DMS probing of RNA-protein interactions, quantitative affinity measurements with truncated protein fragments, complementation assays in yeast RNA (New York, N.Y.) High 21233221
2013 Rrp5 binds pre-rRNA at multiple sites in vivo: the C-terminal domain (CTD) crosslinks to sequences flanking cleavage site A2 and to snoRNAs U3, U14, snR30, and snR10 (required for A0-A2 cleavage), while the N-terminal domain (NTD) crosslinks to sequences flanking site A3 and to the RNA component of RNase MRP. Rrp5 depletion abolishes cotranscriptional cleavage and greatly reduces preribosome compaction. In vivo UV crosslinking and site identification, intramolecular complementation analysis, chromatin spreads (electron microscopy) Molecular cell High 24239293
2016 The DEAD-box protein Rok1, when ATP-bound, stabilizes Rrp5 binding to pre-40S ribosomes; ATP hydrolysis by Rok1 is required for release of Rrp5 from pre-40S ribosomes in vivo, allowing Rrp5 to subsequently participate in 60S subunit assembly. Rrp5 also interacts with the DEAD-box protein Has1, and blocking Rrp5 release from pre-40S subunits causes accumulation of snR30. In vivo and in vitro biochemical analyses; ATP vs ADP-bound Rok1 binding assays; co-immunoprecipitation; genetic experiments with inactivation mutants PLoS biology High 27280440
2018 The crystal structure of the Rrp5 TPR (TetratricoPeptide Repeat) module was solved (PDB: 5NLG). In vitro assays demonstrated that the TPR region alone does not bind RNA, whereas the three S1 domains preceding the TPR module can associate with homopolymeric RNA. Association of Rrp5 constructs with several proposed interactors was tested in support of cryo-EM-based models. X-ray crystallography, in vitro RNA binding assays with domain deletion constructs, protein interaction assays FEBS open bio High 30338212
2019 Rrp5 functions as a checkpoint coupling 40S and 60S ribosome assembly: early in transcription, Rrp5 blocks access of Rcl1 to the nascent rRNA, inhibiting pre-40S rRNA cleavage and separation of the two subunit precursors. Upon transcription of domain I of 25S rRNA, the 60S assembly factors Noc1/Noc2 bind both this RNA and Rrp5, altering Rrp5's RNA-binding mode to allow Rcl1-mediated pre-40S rRNA processing. Noc1 HEAT-repeat domain mutants deficient in subunit separation are rescued by overexpression of wild-type but not catalytically inactive Rcl1. Quantitative RNA binding assays, pre-rRNA cleavage assays, genetic epistasis (Noc1 mutants rescued by Rcl1 overexpression), in vivo co-immunoprecipitation RNA (New York, N.Y.) High 31217256
2002 High-dosage snR10 suppresses defects of a bipartite rrp5 allele in yeast; suppression does not restore cleavage at A2 but improves overall pre-rRNA processing rate and increases active ribosome levels, indicating a functional connection between snR10 and Rrp5 in ribosome biogenesis. Multicopy suppressor screen, phenotypic analysis (growth, temperature sensitivity), Northern blot analysis of pre-rRNA processing, polysome profiling Molecular genetics and genomics Medium 12242501
2005 Human NFBP (PDCD11) physically interacts with HIV-1 Tat protein via Tat residues 37–48, and this interaction is modulated by RNA molecules. NFBP colocalizes with Tat in the nucleus and nucleoli. Functionally, NFBP augments TAR-dependent LTR activation by Tat in the absence of κB-binding sites, but interferes with the synergistic activation of LTR transcription by P65 and Tat together. Co-immunoprecipitation, immunofluorescence colocalization, domain mapping with deletion mutants, LTR reporter transcription assays Journal of cellular physiology Medium 15887232
2020 In zebrafish, PDCD11 is required for microglia differentiation; pdcd11 deficiency prevents maturation of precursors to brain microglia while augmenting inflammatory macrophage brain colonization. Mechanistically, PDCD11 differentially regulates NF-κB family members: suppressing P65-mediated expression of inflammatory cytokines (e.g., tnfα) and enhancing c-Rel-dependent expression of tgfβ1. Zebrafish genetic loss-of-function (pdcd11 deficiency), immunofluorescence, transcriptional pathway analysis, cytokine expression assays Cell death and differentiation Medium 32709934
2022 In Drosophila, Rrp5 (PDCD11 ortholog) localizes to the nucleolus and is required for pre-rRNA processing; depletion of Rok1 causes Rrp5 to become enriched in the core of the nucleolus, indicating that Rok1 is required for accurate subcellular localization of Rrp5 within the nucleolus and for its role in ITS1 and ITS2 rRNA processing. Genetics (rok1 mutant analysis), fluorescence in situ hybridization (FISH) for ITS1/ITS2 signals, immunofluorescence localization of Rrp5 in nucleolus International journal of molecular sciences Medium 35628496
2025 In p53-mutant breast and colon cancer cells, extra-nucleolar PDCD11 binds the transactivation domain (TAD) of C-MYC in the nucleoplasm, preventing SKP2 (an E3 ligase component and transcriptional target of C-MYC) from interacting with and ubiquitinating C-MYC, thereby stabilizing C-MYC and activating downstream signaling for G1/S transition, proliferation, and migration. PDCD11 silencing restores SKP2-mediated C-MYC degradation and suppresses tumor growth and metastasis in vivo. Co-immunoprecipitation, domain mapping of C-MYC TAD interaction, ubiquitination assays, PDCD11 knockdown with C-MYC stability and SKP2 interaction readouts, xenograft mouse tumor models Advanced science Medium 40051297
2025 PDCD11 was identified as a carrier of HBV RNA/DNA into extracellular vesicles in HBV-infected HCC cells; depletion of PDCD11 reduced accumulation of HBV RNAs (pre-genomic RNA, HBx, HBc, HBs mRNAs) and intact virions in EVs. MRPL2 was found to interact with PDCD11 in the nucleus, where MRPL2 nuclear localization enhances intracellular calcium signaling through this interaction. ASO-mediated depletion of PDCD11, qRT-PCR for HBV RNAs in EVs, proteome profiling by LC-MS/MS, protein-protein interaction network analysis, nuclear localization assays Frontiers in cell and developmental biology Low 41425093

Source papers

Stage 0 corpus · 21 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Argonautes ALG-3 and ALG-4 are required for spermatogenesis-specific 26G-RNAs and thermotolerant sperm in Caenorhabditis elegans. Proceedings of the National Academy of Sciences of the United States of America 186 20133686
1996 RRP5 is required for formation of both 18S and 5.8S rRNA in yeast. The EMBO journal 135 8896463
2013 Rrp5 binding at multiple sites coordinates pre-rRNA processing and assembly. Molecular cell 62 24239293
2009 A novel small-subunit processome assembly intermediate that contains the U3 snoRNP, nucleolin, RRP5, and DBP4. Molecular and cellular biology 59 19332556
2021 CircRNA circ-PDCD11 promotes triple-negative breast cancer progression via enhancing aerobic glycolysis. Cell death discovery 41 34420029
2016 The DEAD-box Protein Rok1 Orchestrates 40S and 60S Ribosome Assembly by Promoting the Release of Rrp5 from Pre-40S Ribosomes to Allow for 60S Maturation. PLoS biology 38 27280440
2003 Kinetics and mechanism of iron release from the bacterial ferric binding protein nFbp: exogenous anion influence and comparison with mammalian transferrin. Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry 24 14551810
2011 The roles of S1 RNA-binding domains in Rrp5's interactions with pre-rRNA. RNA (New York, N.Y.) 22 21233221
2017 Elevation of autoantibody level against PDCD11 in patients with transient ischemic attack. Oncotarget 21 29507658
2008 Evidence for involvement of NFBP in processing of ribosomal RNA. Journal of cellular physiology 15 17654514
2005 Interplay between NFBP and NF-kappaB modulates tat activation of the LTR. Journal of cellular physiology 15 15887232
2019 Rrp5 establishes a checkpoint for 60S assembly during 40S maturation. RNA (New York, N.Y.) 14 31217256
2020 Yolk sac-derived Pdcd11-positive cells modulate zebrafish microglia differentiation through the NF-κB-Tgfβ1 pathway. Cell death and differentiation 13 32709934
2025 PDCD11 Stabilizes C-MYC Oncoprotein by Hindering C-MYC-SKP2 Negative Feedback Loop to Facilitate Progression of p53-Mutant Breast and Colon Malignancies. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 7 40051297
2017 Rare PDCD11 variations are not associated with risk of schizophrenia in Japan. Psychiatry and clinical neurosciences 7 28657695
2021 Meiotic H3K9me2 distribution is influenced by the ALG-3 and ALG-4 pathway and by poly(U) polymerase activity. microPublication biology 6 34549171
2002 High dosage of the small nucleolar RNA snR10 specifically suppresses defects of a yeast rrp5 mutant. Molecular genetics and genomics : MGG 5 12242501
2018 Structural and interaction analysis of the Rrp5 C-terminal region. FEBS open bio 3 30338212
2026 Lometrexol targets MRPL2 to suppress NSCLC via dual regulation of mitochondrial ribosomal activity and nuclear PDCD11/ Ca2+ signaling. Bioorganic chemistry 2 41558196
2022 The DEAD-Box Protein Rok1 Coordinates Ribosomal RNA Processing in Association with Rrp5 in Drosophila. International journal of molecular sciences 1 35628496
2025 Proteome profiling of extracellular vesicles-derived from hepatitis B virus-infected hepatocellular carcinoma cell lines identifies PDCD11 as a carrier of viral RNAs. Frontiers in cell and developmental biology 0 41425093

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