GO:0070545 PeBoW complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0070545 (PeBoW complex) is a conserved nucleolar protein complex that coordinates ribosome biogenesis with cell cycle progression.
• In human cells the PeBoW complex is composed of Pes1, Bop1 and WDR12; in Saccharomyces cerevisiae the orthologous proteins are Nop7p, Erb1 and Ytm1.
• The complex is required for maturation of the 60S ribosomal subunit, and its integrity controls nucleolar localization and assembly of its own subunits.
• Dominant-negative Pes1 mutants are incorporated into the PeBoW complex and inhibit ribosomal RNA processing and cell proliferation.
• The DEAD-box helicase DDX27 stably associates with the PeBoW complex and regulates 3' end formation of ribosomal 47S RNA.
• PeBoW components are implicated in cancer, failing hearts and longevity-promoting mitochondrial unfolded protein response activation [1,4,6,7].
Description
The PeBoW complex (GO:0070545) is a nucleolar protein complex that coordinates ribosome biogenesis with cell cycle progression. It was originally identified in mammalian cells as a Pes1-Bop1 complex to which WDR12 was subsequently added, defining the three-subunit PeBoW assembly. The same functional module exists in Saccharomyces cerevisiae, where the orthologous proteins are known as Nop7p, Erb1 and Ytm1. Because ribosome production is tightly coupled to cell growth and division, the PeBoW complex sits at a critical regulatory node that links nucleolar RNA processing to proliferative capacity [3,5]. Researchers study GO:0070545 to understand how 60S ribosomal subunit maturation is controlled, how nucleolar stress is sensed, and how disruption of this complex contributes to cancer, cardiac disease and other human disorders [1,3,7].
PeBoW complex At A Glance
| GO ID | GO:0070545 |
|---|---|
| GO term | PeBoW complex |
| Ontology | cellular_component |
| Synonym | None listed in QuickGO |
| Major function | Coordinates ribosome biogenesis with cell cycle progression and is required for 60S ribosomal subunit maturation |
| Human subunits | Pes1, Bop1, WDR12 [3,8] |
| Yeast orthologs | Nop7p, Erb1, Ytm1 |
| Subcellular location | Nucleolus |
| Associated factor | DEAD-box helicase DDX27 stably associates with the complex |
What Is GO:0070545?
GO:0070545 describes a protein complex involved in coordinating ribosome biogenesis with cell cycle progression. In human cells it is composed of Pes1, Bop1 and WDR12; in Saccharomyces the corresponding proteins are Nop7p, Erb1 and Ytm1. The complex localizes to the nucleolus and is required for maturation of the 60S ribosomal subunit.
Why Is PeBoW complex Important in Cell Biology?
The PeBoW complex is important because it couples the production of the 60S ribosomal subunit to cell cycle progression, making it a central hub for controlling cell growth and proliferation. Disruption of PeBoW subunits impairs ribosomal RNA processing and blocks proliferation, while dominant-negative Pes1 mutants are incorporated into the complex and inhibit these processes. Because ribosome biogenesis is frequently deregulated in cancer and other diseases, the PeBoW complex is a relevant target for mechanistic studies and for understanding how nucleolar stress signals to the rest of the cell [1,3,6].
• Required for maturation of the 60S ribosomal subunit.
• Coordinates ribosome biogenesis with cell cycle progression.
• Controls nucleolar localization and assembly of its own subunits.
• Dominant-negative Pes1 mutants inhibit rRNA processing and cell proliferation via incorporation into the complex.
• DDX27 associates with the PeBoW complex and regulates 3' end formation of 47S rRNA.
• WDR12 is up-regulated in failing hearts and causes deterioration of cardiac function.
• SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer, implicating PeBoW-related pathways.
• Targeting BRIX1 via engineered exosomes induces nucleolar stress to suppress cancer progression.
• Elements of the PeBoW complex are required for longevity-promoting mitochondrial unfolded protein response activation.
• PeBoW components are candidate biomarkers and therapeutic targets in proliferative and cardiac diseases [1,6,7].
PeBoW complex: Components, Assembly and Research Methods
Assembly and interdependence of Pes1, Bop1 and WDR12
In simple terms: The three PeBoW proteins need each other to find the nucleolus and build a working complex.
In human cells, Pes1, Bop1 and WDR12 are interdependent for nucleolar localization and assembly of the PeBoW complex. WDR12 was identified as a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation. Dominant-negative Pes1 mutants are incorporated into the PeBoW complex and inhibit ribosomal RNA processing and cell proliferation, showing that subunit composition directly determines complex function.
Role in 60S ribosomal subunit maturation
In simple terms: The PeBoW complex helps build the large ribosomal subunit by processing ribosomal RNA.
The PeBoW complex is required for maturation of the 60S ribosomal subunit. Its subunits control nucleolar localization and assembly, and loss of any subunit impairs ribosomal RNA processing. DDX27, a DEAD-box helicase, stably associates with the PeBoW complex and regulates 3' end formation of ribosomal 47S RNA, linking the complex to early rRNA processing steps.
Coupling ribosome biogenesis to cell cycle progression
In simple terms: The PeBoW complex acts as a checkpoint that ties ribosome production to cell division.
The PeBoW complex coordinates ribosome biogenesis with cell cycle progression. Dominant-negative Pes1 mutants inhibit both ribosomal RNA processing and cell proliferation, demonstrating that the complex couples these processes. WDR12 is required for ribosome biogenesis and cell proliferation, reinforcing the link between PeBoW function and proliferative capacity.
Associated factors and regulatory inputs
In simple terms: Other proteins and cellular stresses can influence how the PeBoW complex works.
DDX27 stably associates with the PeBoW complex and regulates 3' end formation of ribosomal 47S RNA. SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer, indicating that redox and oncogenic signaling can influence PeBoW-related ribosome production. Elements of the PeBoW complex are required for longevity-promoting mitochondrial unfolded protein response activation, showing that the complex integrates mitochondrial stress signals.
Nucleolar stress and disease connections
In simple terms: When the PeBoW complex is disrupted, cells experience nucleolar stress that can suppress cancer growth.
Targeting BRIX1 via engineered exosomes induces nucleolar stress to suppress cancer progression, highlighting the therapeutic potential of interfering with ribosome biogenesis pathways that include PeBoW components. WDR12, a member of the nucleolar PeBoW complex, is up-regulated in failing hearts and causes deterioration of cardiac function. These findings link PeBoW complex biology to both cancer and cardiac disease [1,7].
Key Genes Involved in GO:0070545 PeBoW complex
The following genes and proteins are the core components and key associated factors of the PeBoW complex (GO:0070545) and its regulatory network.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PES1 | Core PeBoW subunit; required for nucleolar localization and assembly | Dominant-negative mutants inhibit rRNA processing and proliferation |
| BOP1 | Core PeBoW subunit; required for 60S maturation | Interdependence with Pes1 and WDR12 controls complex assembly |
| WDR12 | Core PeBoW subunit; required for ribosome biogenesis and proliferation | Up-regulated in failing hearts and causes cardiac dysfunction |
| DDX27 | DEAD-box helicase stably associated with PeBoW; regulates 3' end formation of 47S rRNA | Links PeBoW to early rRNA processing |
| NOP7 | Yeast ortholog of Pes1; PeBoW component | Model for conserved PeBoW function |
| ERB1 | Yeast ortholog of Bop1; PeBoW component | Model for conserved PeBoW function |
| YTM1 | Yeast ortholog of WDR12; PeBoW component | Model for conserved PeBoW function |
| BRIX1 | Ribosome biogenesis factor; targeting induces nucleolar stress | Therapeutic target in cancer via engineered exosomes |
| SOD1 | Regulates ribosome biogenesis in KRAS mutant NSCLC | Links redox signaling to PeBoW-related pathways |
| KRAS | Oncogenic driver in NSCLC; context for SOD1-ribosome axis | Model for PeBoW-related cancer biology |
| MT-UPR genes | Mitochondrial unfolded protein response effectors requiring PeBoW elements | Link PeBoW to longevity and mitochondrial stress |
| PES1 (dominant-negative) | Incorporated into PeBoW; inhibits rRNA processing | Tool to dissect PeBoW function |
| BOP1 (mutant) | Interferes with PeBoW assembly | Tool to study nucleolar localization |
| WDR12 (overexpression) | Causes cardiac deterioration in models | Model for cardiac disease |
| DDX27 (depletion) | Alters 47S rRNA 3' end formation | Tool to study rRNA processing |
| BRIX1 (targeted) | Induces nucleolar stress and suppresses cancer | Exosome-based therapeutic model |
| PeBoW complex (intact) | Coordinates ribosome biogenesis with cell cycle | Central node for proliferation studies |
How Is PeBoW complex Regulated?
The PeBoW complex is regulated at the level of subunit interdependence: Pes1, Bop1 and WDR12 control each other's nucleolar localization and assembly, so loss of one subunit disrupts the entire complex. Dominant-negative Pes1 mutants are incorporated into the complex and inhibit rRNA processing and proliferation, indicating that subunit composition and stoichiometry are critical for function. DDX27 stably associates with the PeBoW complex and regulates 3' end formation of 47S rRNA, providing an additional layer of processing control. SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer, linking oncogenic and redox signaling to PeBoW-related ribosome production. Elements of the PeBoW complex are required for longevity-promoting mitochondrial unfolded protein response activation, showing that mitochondrial stress pathways can influence PeBoW-dependent processes.
PeBoW complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| BRIX1 | Cancer progression; nucleolar stress | Engineered exosome delivery in cancer models |
| WDR12 | Failing hearts; cardiac dysfunction | Cardiac overexpression or KO models |
| SOD1 | KRAS mutant non-small cell lung cancer | KRAS mutant NSCLC cell lines |
| PES1 | Proliferation and rRNA processing defects | Dominant-negative Pes1 expression models |
| PeBoW complex | Ribosome biogenesis and cell cycle coordination | Subunit KO and rescue models |
Cancer and nucleolar stress
Targeting BRIX1 via engineered exosomes induces nucleolar stress to suppress cancer progression, demonstrating that interfering with ribosome biogenesis pathways that include PeBoW components can have therapeutic benefit. SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer, implicating PeBoW-related ribosome production in oncogenic signaling. Because the PeBoW complex coordinates ribosome biogenesis with cell cycle progression, its subunits are candidate targets in proliferative diseases.
Cardiac disease
WDR12, a member of the nucleolar PeBoW complex, is up-regulated in failing hearts and causes deterioration of cardiac function. This links PeBoW complex biology to heart failure and suggests that WDR12 levels may be relevant to cardiac pathophysiology.
Longevity and mitochondrial stress
Longevity-promoting mitochondrial unfolded protein response activation requires elements of the PeBoW complex, connecting the complex to mitochondrial stress signaling and aging-related pathways.
From PeBoW complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a PeBoW subunit impair 60S maturation? | Knockout of PES1, BOP1 or WDR12 in human cell lines |
| Does a dominant-negative Pes1 mutant inhibit proliferation? | Point mutation or dominant-negative Pes1 expression |
| Does WDR12 overexpression affect cardiac function? | Knock-in or overexpression in cardiac models |
| Where does the PeBoW complex localize? | Tagged knock-in of Pes1, Bop1 or WDR12 for imaging |
| Does DDX27 association require intact PeBoW? | Knockout of PeBoW subunits followed by DDX27 co-IP |
| Does PeBoW support mitochondrial UPR and longevity? | Knockout of PeBoW elements in longevity models |
How to Study the PeBoW complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Northern blot / rRNA labeling | rRNA processing intermediates | Assess 60S maturation defects |
| Co-immunoprecipitation | Protein-protein interactions | Detect PeBoW subunits and DDX27 [2,8] |
| Mass spectrometry | Complex composition | Identify associated factors |
| Fluorescence microscopy | Nucleolar localization | Test subunit interdependence |
| Proliferation assay | Cell growth | Link PeBoW to cell cycle [3,5] |
| 3' end mapping | 47S rRNA 3' end formation | Study DDX27 function |
| CRISPR knockout | Gene function | Dissect PeBoW subunit roles |
| Exosome delivery | Targeted protein depletion | Induce nucleolar stress in cancer |
Ribosomal RNA processing assays
Ribosomal RNA processing can be monitored by northern blotting or metabolic labeling to detect 47S, 45S and 32S intermediates, as used to show that PeBoW subunits are required for 60S maturation. DDX27 association with the PeBoW complex regulates 3' end formation of 47S rRNA, which can be assayed by 3' end mapping.
Proteomics and co-immunoprecipitation
Co-immunoprecipitation and mass spectrometry can identify PeBoW subunits and associated factors such as DDX27 [2,8]. Interdependence of Pes1, Bop1 and WDR12 for complex assembly can be tested by knocking down each subunit and monitoring the others.
Imaging of nucleolar localization
Fluorescence microscopy of tagged Pes1, Bop1 or WDR12 can assess nucleolar localization and assembly, which depends on the interdependence of the three subunits.
Functional proliferation assays
Cell proliferation assays after PeBoW subunit perturbation reveal the coupling of ribosome biogenesis to cell cycle progression [3,5]. Dominant-negative Pes1 mutants inhibit proliferation, providing a functional readout.
How CRISPR Can Be Used to Study GO:0070545 PeBoW complex
Knockout
CRISPR knockout of PES1, BOP1 or WDR12 can be used to test the requirement for each subunit in 60S ribosomal subunit maturation and cell proliferation, as demonstrated by interdependence studies. Knockout of PeBoW elements can also test their role in longevity-promoting mitochondrial unfolded protein response activation.
Point Mutation
Point mutations that create dominant-negative Pes1 alleles can be introduced to mimic the inhibitory effects on ribosomal RNA processing and cell proliferation observed with dominant-negative Pes1 mutants.
Knock-in
Tagged knock-in of Pes1, Bop1 or WDR12 allows visualization of nucleolar localization and assembly of the PeBoW complex in live cells. Knock-in of WDR12 variants can be used to model cardiac effects of WDR12 up-regulation.
Overexpression
Overexpression of WDR12 causes deterioration of cardiac function in models, providing a gain-of-function system to study PeBoW-related cardiac disease. Overexpression of PeBoW subunits can also be used to test whether increased ribosome biogenesis drives proliferation.
How EDITGENE Supports PeBoW complex Research
Researchers studying PeBoW complex-related genes often need to determine whether a candidate gene is causally involved in ribosome biogenesis, cell cycle coordination or disease phenotypes. EDITGENE provides CRISPR-based cell model services that enable precise perturbation of PeBoW components and their associated factors.
Contact EDITGENE today to design your custom CRISPR model for PeBoW complex research.
Frequently Asked Questions About PeBoW complex
What is the PeBoW complex?
The PeBoW complex (GO:0070545) is a nucleolar protein complex that coordinates ribosome biogenesis with cell cycle progression and is required for 60S ribosomal subunit maturation.
What genes are involved in the PeBoW complex?
In human cells the core genes are PES1, BOP1 and WDR12; in Saccharomyces the orthologs are NOP7, ERB1 and YTM1.
Where is the PeBoW complex located?
The PeBoW complex localizes to the nucleolus.
What is the function of WDR12?
WDR12 is a member of the PeBoW complex required for ribosome biogenesis and cell proliferation, and it is up-regulated in failing hearts [7,8].
How is the PeBoW complex assembled?
Pes1, Bop1 and WDR12 are interdependent for nucleolar localization and assembly of the complex.
What happens when PeBoW complex subunits are mutated?
Dominant-negative Pes1 mutants are incorporated into the complex and inhibit ribosomal RNA processing and cell proliferation.
Does DDX27 interact with the PeBoW complex?
Yes, the DEAD-box helicase DDX27 stably associates with the PeBoW complex and regulates 3' end formation of 47S rRNA.
Is the PeBoW complex involved in cancer?
Targeting BRIX1 induces nucleolar stress to suppress cancer progression, and SOD1 regulates ribosome biogenesis in KRAS mutant lung cancer, linking PeBoW-related pathways to cancer [1,6].
Is the PeBoW complex linked to heart disease?
WDR12, a PeBoW component, is up-regulated in failing hearts and causes deterioration of cardiac function.
How can I study the PeBoW complex with CRISPR?
CRISPR knockout, point mutation, knock-in and overexpression models can be used to dissect PeBoW subunit function in ribosome biogenesis and disease [3,5,7].
Conclusion
The PeBoW complex (GO:0070545) is a conserved nucleolar machine that couples 60S ribosomal subunit maturation to cell cycle progression through the interdependent action of Pes1, Bop1 and WDR12. Its dysfunction is linked to cancer, cardiac disease and longevity-related mitochondrial stress pathways [1,4,7]. CRISPR-based models provide a precise way to dissect the causal roles of PeBoW components and their associated factors in health and disease [3,5].
References
- 1. Gan Y et al.. 2024. Targeting BRIX1 via Engineered Exosomes Induces Nucleolar Stress to Suppress Cancer Progression.. Adv Sci (Weinh) 11(47):e2407370 PMID: 39475053
- 2. Kellner M et al.. 2015. DEAD-box helicase DDX27 regulates 3' end formation of ribosomal 47S RNA and stably associates with the PeBoW-complex.. Exp Cell Res 334(1):146-59 PMID: 25825154
- 3. Rohrmoser M et al.. 2007. Interdependence of Pes1, Bop1, and WDR12 controls nucleolar localization and assembly of the PeBoW complex required for maturation of the 60S ribosomal subunit.. Mol Cell Biol 27(10):3682-94 PMID: 17353269
- 4. Adedoja A et al.. 2026. Longevity-promoting mitochondrial unfolded protein response activation requires elements of the PeBoW complex.. Genes Dev 40(1-2):110-123 PMID: 41162154
- 5. Grimm T et al.. 2006. Dominant-negative Pes1 mutants inhibit ribosomal RNA processing and cell proliferation via incorporation into the PeBoW-complex.. Nucleic Acids Res 34(10):3030-43 PMID: 16738141
- 6. Wang X et al.. 2021. SOD1 regulates ribosome biogenesis in KRAS mutant non-small cell lung cancer.. Nat Commun 12(1):2259 PMID: 33859191
- 7. Moilanen AM et al.. 2015. WDR12, a Member of Nucleolar PeBoW-Complex, Is Up-Regulated in Failing Hearts and Causes Deterioration of Cardiac Function.. PLoS One 10(4):e0124907 PMID: 25915632
- 8. Hölzel M et al.. 2005. Mammalian WDR12 is a novel member of the Pes1-Bop1 complex and is required for ribosome biogenesis and cell proliferation.. J Cell Biol 170(3):367-78 PMID: 16043514
