GO:0160232 INTAC complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0160232 (INTAC complex) is a cellular component defined as a protein complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC) that stably associates with the C-terminus of RNA polymerase II and promotes premature RNA polymerase II transcription termination.
• INTAC was identified as an RNA polymerase II phosphatase that removes phosphorylation marks from the RNA polymerase II C-terminal domain to trigger transcription termination.
• The complex includes Integrator subunits and PP2A-AC, and its integrity depends on factors such as DSS1.
• INTAC functions in promoter-proximal premature termination and is linked to chromatin context and genome maintenance.
• INTAC activity can influence sensitivity to BET inhibitors, revealing catalytic-independent functions.
• Research on INTAC uses knockout, point-mutation, knock-in, and overexpression models, combined with transcriptomics, proteomics, and imaging [1,2,3,6].
Description
The INTAC complex (Integrator-PP2A complex) is a cellular component that couples RNA polymerase II (RNAPII) phosphorylation status to premature transcription termination. It was identified as a stable complex containing Integrator subunits and the protein phosphatase 2A core enzyme (PP2A-AC), and it associates with the C-terminal domain (CTD) of RNAPII. This association allows INTAC to act as an RNAPII phosphatase, removing phosphorylation marks that are otherwise associated with productive elongation. The discovery of INTAC provided a molecular explanation for how premature termination is controlled at promoter-proximal regions. Because transcription termination is a critical step in gene regulation, the INTAC complex has become a focus for researchers studying RNAPII dynamics, chromatin context, and genome maintenance. INTAC is also implicated in modulating sensitivity to BET inhibitors, suggesting that its functions extend beyond its catalytic phosphatase activity. The complex is required for proper Integrator-PP2A function, and its integrity is supported by accessory factors such as DSS1. Understanding INTAC requires integrating structural, biochemical, and functional data. The complex is composed of multiple subunits, and its assembly and activity are regulated in a context-dependent manner [1,5]. This article summarizes the current knowledge of INTAC based on QuickGO annotation and verified PubMed literature, and outlines experimental approaches for studying its components, assembly, and functions.
INTAC complex At A Glance
| GO ID | GO:0160232 |
|---|---|
| GO term | INTAC complex |
| Ontology | cellular_component |
| Synonym | integrator-PP2A complex |
| Major function | Promotes premature RNA polymerase II transcription termination by acting as an RNAPII phosphatase |
| Complex components | Integrator subunits and protein phosphatase 2A core enzyme (PP2A-AC) |
| Association | Stably associates with the C-terminus of RNA polymerase II |
| Related factor | DSS1 is required for proper Integrator-PP2A function |
| Disease relevance | Linked to cancer biology through sensitivity to BET inhibition |
What Is GO:0160232?
According to the Gene Ontology, GO:0160232 (INTAC complex) is a protein complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC) that stably associates with the C-terminus of RNA polymerase II and promotes premature RNA polymerase II transcription termination. In simpler terms, INTAC is a molecular machine that binds to the tail of RNA polymerase II and removes phosphate groups, causing transcription to stop early.
Why Is INTAC complex Important in Cell Biology?
The INTAC complex is important because it provides a direct link between RNA polymerase II phosphorylation and premature transcription termination, a key regulatory step in gene expression. Dysregulation of termination can lead to altered gene expression programs that contribute to diseases such as cancer. INTAC also integrates promoter-proximal termination with chromatin context and genome maintenance, making it relevant to genome stability. Understanding INTAC function may reveal new therapeutic vulnerabilities, particularly in cancers sensitive to BET inhibitors.
• INTAC is a major RNA polymerase II phosphatase that controls premature termination.
• It couples transcription termination to the phosphorylation state of the RNAPII C-terminal domain.
• INTAC integrity depends on factors such as DSS1, linking it to broader protein quality control.
• The complex modulates sensitivity to BET inhibitors, suggesting roles in cancer therapy.
• INTAC functions in promoter-proximal termination and is connected to chromatin context.
• It influences processive transcription elongation through CDK12 and LEO1 phosphorylation.
• IntS6 and the Integrator phosphatase module tune the efficiency of select premature termination events.
• INTAC has catalytic-independent functions that affect cellular responses.
• The complex is relevant to genome maintenance and stability.
• Studying INTAC requires integrated approaches including CRISPR models and multi-omics [1,2,3].
INTAC complex: Components, Assembly and Research Methods
What Happens During INTAC complex?
In simple terms: INTAC binds to the tail of RNA polymerase II and removes phosphate marks, causing transcription to stop early.
The INTAC complex promotes premature RNA polymerase II transcription termination by acting as an RNAPII phosphatase. It stably associates with the C-terminus of RNA polymerase II and dephosphorylates specific residues on the RNAPII C-terminal domain, thereby triggering termination. This activity is particularly important at promoter-proximal regions, where premature termination helps regulate gene expression. INTAC also integrates this termination function with chromatin context and genome maintenance.
Structure and Composition of INTAC complex
In simple terms: INTAC is made of Integrator proteins and a PP2A core enzyme, and it needs DSS1 to work properly.
The INTAC complex contains Integrator subunits and the protein phosphatase 2A core enzyme (PP2A-AC). The Integrator subunits provide a platform for interaction with RNA polymerase II, while PP2A-AC provides the catalytic phosphatase activity. DSS1 is required for proper Integrator-PP2A function, indicating that accessory factors are essential for complex integrity. The complex stably associates with the C-terminus of RNA polymerase II, which positions it to act on the RNAPII C-terminal domain.
Molecular Mechanism of INTAC complex
In simple terms: INTAC removes phosphate groups from RNA polymerase II, which acts like a switch to stop transcription.
INTAC functions as an RNA polymerase II phosphatase, removing phosphorylation marks from the RNAPII C-terminal domain. This dephosphorylation promotes premature transcription termination. The complex also modulates LEO1 phosphorylation in coordination with CDK12, affecting processive transcription elongation. IntS6 and the Integrator phosphatase module tune the efficiency of select premature termination events, indicating substrate specificity. Catalytic-independent functions of INTAC have also been described, conferring sensitivity to BET inhibition.
Regulation of INTAC complex
In simple terms: INTAC activity is adjusted by other proteins and cellular signals to meet the cell's needs.
The activity and assembly of the INTAC complex are regulated by its subunits and accessory factors such as DSS1. CDK12 modulates LEO1 phosphorylation in coordination with INTAC, linking INTAC function to the broader transcription elongation machinery. The phosphatase PP1 also regulates RNA polymerase II pause release, indicating that multiple phosphatases contribute to RNAPII regulation. INTAC integrates promoter-proximal premature termination with chromatin context and genome maintenance, suggesting that its regulation is context-dependent.
Key Genes Involved in GO:0160232 INTAC complex
The following genes and proteins are key components or regulators of the INTAC complex and its associated functions.
| Gene | Major Role | Research Relevance |
|---|---|---|
| INTS1 | Integrator subunit | Component of INTAC complex |
| INTS2 | Integrator subunit | Component of INTAC complex |
| INTS3 | Integrator subunit | Component of INTAC complex |
| INTS4 | Integrator subunit | Component of INTAC complex |
| INTS5 | Integrator subunit | Component of INTAC complex |
| INTS6 | Integrator subunit | Tune efficiency of premature termination |
| INTS7 | Integrator subunit | Component of INTAC complex |
| INTS8 | Integrator subunit | Component of INTAC complex |
| INTS9 | Integrator subunit | Component of INTAC complex |
| INTS10 | Integrator subunit | Component of INTAC complex |
| INTS11 | Integrator subunit | Component of INTAC complex |
| INTS12 | Integrator subunit | Component of INTAC complex |
| PPP2CA | PP2A catalytic subunit | Provides phosphatase activity |
| PPP2R1A | PP2A scaffold subunit | Component of PP2A-AC |
| DSS1 | Accessory factor | Required for proper Integrator-PP2A function |
| CDK12 | Kinase | Modulates LEO1 phosphorylation with INTAC |
| LEO1 | Transcription elongation factor | Phosphorylation regulated by CDK12/INTAC |
| POLR2A | RNA polymerase II largest subunit | Contains C-terminal domain targeted by INTAC |
How Is INTAC complex Regulated?
The INTAC complex is regulated at multiple levels. Its assembly and stability depend on accessory factors such as DSS1. Its activity is coordinated with kinases like CDK12, which modulates LEO1 phosphorylation and processive transcription elongation. The phosphatase PP1 also contributes to RNA polymerase II pause release, indicating that INTAC functions within a network of phosphatases. Additionally, INTAC integrates promoter-proximal premature termination with chromatin context and genome maintenance, suggesting that its regulation is influenced by chromatin state and genome integrity pathways.
INTAC complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| INTS6 | Premature termination efficiency | Knockout cell lines |
| PPP2CA | Phosphatase activity in cancer | Point mutation models |
| DSS1 | Integrator-PP2A function | Knockout and rescue models |
| CDK12 | Transcription elongation and cancer | Knockout and inhibitor studies |
| POLR2A | RNAPII CTD phosphorylation | Knock-in of phospho-mutants |
INTAC complex and Cancer
The INTAC complex has been linked to cancer biology through its role in modulating sensitivity to BET inhibitors. Catalytic-independent functions of INTAC confer sensitivity to BET inhibition, suggesting that INTAC status could influence therapeutic responses. Dysregulation of transcription termination pathways, in which INTAC plays a central role, can contribute to oncogenic gene expression programs [1,5].
INTAC complex and Genome Maintenance
INTAC integrates promoter-proximal premature termination with chromatin context and genome maintenance. This connection suggests that loss of INTAC function could impact genome stability, although direct disease associations require further study.
INTAC complex and Transcription-Related Disorders
Given its core role in RNA polymerase II regulation, INTAC dysfunction may contribute to disorders characterized by transcriptional misregulation. However, specific human diseases caused by INTAC mutations are not yet well defined in the verified literature [1,3].
From INTAC complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of INTAC in transcription termination? | Knockout of Integrator subunits |
| How does PP2A catalytic activity contribute to INTAC function? | Point mutation of PPP2CA |
| What are the catalytic-independent functions of INTAC? | Knock-in of catalytically dead PP2A |
| How does DSS1 regulate INTAC assembly? | Knockout and tagged knock-in of DSS1 |
| How does INTAC coordinate with CDK12? | Knockout of CDK12 and LEO1 phospho-mutants |
| What is the effect of INTAC overexpression? | Overexpression of Integrator subunits |
How to Study the INTAC complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Gene expression changes | Assess termination defects |
| Ribo-seq | Translation efficiency | Measure effects on protein synthesis |
| Phosphoproteomics | Phosphorylation of RNAPII CTD | Determine INTAC substrate specificity |
| ChIP-seq | RNAPII occupancy | Map premature termination sites |
| Co-IP / Mass spectrometry | Protein interactions | Identify INTAC subunits and partners |
| CRISPR screen | Genetic vulnerabilities | Find modifiers of BET inhibitor sensitivity |
| Immunofluorescence | Protein localization | Visualize INTAC components |
Transcriptomics and Ribo-seq
RNA-seq and Ribo-seq can measure changes in transcription and translation upon INTAC perturbation [1,2]. These methods help identify genes whose premature termination depends on INTAC.
Proteomics and Phosphoproteomics
Mass spectrometry-based proteomics can identify INTAC subunits and interacting partners, while phosphoproteomics can reveal changes in RNAPII CTD phosphorylation [1,6].
Imaging and Chromatin Analysis
Imaging approaches can visualize INTAC localization, and chromatin immunoprecipitation (ChIP) can assess RNAPII occupancy and termination defects.
CRISPR Screening
CRISPR library screening can identify genes that modulate sensitivity to BET inhibitors in the context of INTAC function.
How CRISPR Can Be Used to Study GO:0160232 INTAC complex
Knockout
CRISPR knockout of Integrator subunits or PP2A components can disrupt INTAC function and reveal its role in transcription termination [1,7]. Knockout models are useful for assessing loss-of-function phenotypes in cancer and genome maintenance [2,5].
Point Mutation
Point mutations in the catalytic domain of PPP2CA can abolish phosphatase activity while preserving complex assembly, allowing separation of catalytic and non-catalytic functions [1,2].
Knock-in
Knock-in of tagged Integrator subunits or phospho-mutant RNAPII CTD can facilitate localization and functional studies [1,6].
Overexpression
Overexpression of INTAC components can be used to study gain-of-function effects on transcription termination and cell viability.
How EDITGENE Supports INTAC complex Research
Researchers studying INTAC complex-related genes often need to determine whether a candidate gene is causally involved in transcription termination, cancer sensitivity, or genome maintenance. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such studies with high precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for INTAC complex research.
Frequently Asked Questions About INTAC complex
What is the INTAC complex?
The INTAC complex (Integrator-PP2A complex) is a protein complex that contains Integrator and PP2A core enzyme and promotes premature RNA polymerase II transcription termination.
What genes are involved in the INTAC complex?
Genes encoding Integrator subunits (INTS1-INTS12), PP2A subunits (PPP2CA, PPP2R1A), and accessory factors such as DSS1 are involved [1,3].
What is the function of GO:0160232?
GO:0160232 describes a protein complex that stably associates with the C-terminus of RNA polymerase II and promotes premature transcription termination.
How does INTAC regulate transcription?
INTAC acts as an RNA polymerase II phosphatase, removing phosphorylation marks from the RNAPII C-terminal domain to trigger termination.
What diseases are associated with INTAC complex?
INTAC has been linked to cancer sensitivity to BET inhibitors and genome maintenance [2,5].
What is the role of DSS1 in INTAC?
DSS1 is required for proper Integrator-PP2A function.
How can I study INTAC complex in the lab?
CRISPR knockout, point mutation, knock-in, and overexpression models combined with RNA-seq, proteomics, and imaging are commonly used [1,2,3].
What is the relationship between INTAC and CDK12?
CDK12 and INTAC modulate LEO1 phosphorylation for processive transcription elongation.
What are catalytic-independent functions of INTAC?
INTAC has functions beyond its phosphatase activity that confer sensitivity to BET inhibition.
What methods are used to study INTAC?
RNA-seq, Ribo-seq, ChIP-seq, phosphoproteomics, and CRISPR screens are used [1,2,5].
Conclusion
The INTAC complex (GO:0160232) is a key regulator of RNA polymerase II transcription termination, acting as a phosphatase that removes phosphorylation marks from the RNAPII C-terminal domain. Its components, including Integrator subunits and PP2A-AC, are essential for its function, and accessory factors such as DSS1 support its integrity. INTAC is implicated in cancer biology and genome maintenance, making it a promising target for further research [2,5]. Studying INTAC requires integrated experimental approaches, including CRISPR-based models and multi-omics. EDITGENE provides comprehensive services to support such research, from knockout and knock-in cell models to library screening and bioinformatics.
References
- 1. Zheng H et al.. 2020. Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase.. Science 370(6520) PMID: 33243860
- 2. Fan P et al.. 2025. Catalytic-independent functions of the Integrator-PP2A complex (INTAC) confer sensitivity to BET inhibition.. Nat Chem Biol 21(6):959-970 PMID: 39809894
- 3. Xu C et al.. 2025. DSS1 is required for proper Integrator-PP2A function.. Nat Commun 16(1):6206 PMID: 40617815
- 4. Wang Z et al.. 2024. The phosphatase PP1 sustains global transcription by promoting RNA polymerase II pause release.. Mol Cell 84(24):4824-4842.e7 PMID: 39603240
- 5. Song A et al.. 2025. The Integrator-PP2A complex integrates promoter-proximal premature termination with chromatin context and genome maintenance.. Trends Biochem Sci 50(12):1118-1130 PMID: 41076348
- 6. Qiu M et al.. 2023. CDK12 and Integrator-PP2A complex modulates LEO1 phosphorylation for processive transcription elongation.. Sci Adv 9(20):eadf8698 PMID: 37205756
- 7. Fujiwara R et al.. 2023. IntS6 and the Integrator phosphatase module tune the efficiency of select premature transcription termination events.. Mol Cell 83(24):4445-4460.e7 PMID: 37995689
