GO:0005847 mRNA cleavage and polyadenylation specificity factor complex: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005847 describes the mRNA cleavage and polyadenylation specificity factor (CPSF) complex, a multisubunit machine that binds the canonical AAUAAA hexamer and U-rich upstream elements on pre-mRNA to stimulate efficient 3' end processing.
• The CPSF complex is essential for cleavage of pre-mRNA at the poly(A) site and for addition of the poly(A) tail, a step required for mRNA stability, export, and translation.
• CPSF6, a key subunit, mediates HIV-1 integration into genes and promotes HIV-1 preintegration complex function, linking CPSF to viral latency and host-pathogen interactions [1,3,8].
• In plants, CPSF73 and CPSF100 are required for efficient polyadenylation and transcription termination, and their inhibition by AN3661 reveals essential biological functions [2,6].
• CPSF6 also mediates nuclear import of human bocavirus 1 NP1 protein and modulates viral capsid protein expression, showing broader roles in DNA virus biology.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable precise dissection of CPSF subunit functions in RNA processing, viral infection, and disease [1,2,5].
Description
The mRNA cleavage and polyadenylation specificity factor (CPSF) complex, annotated as GO:0005847, is a multisubunit cellular component that binds to the canonical AAUAAA hexamer and to U-rich upstream sequence elements on pre-mRNA, thereby stimulating the otherwise weakly active and nonspecific polymerase to elongate efficiently RNAs containing a poly(A) signal. This complex is a central hub for 3' end processing of nearly all eukaryotic messenger RNAs, and its activity is required for the cleavage of pre-mRNA at the poly(A) site and the subsequent addition of the poly(A) tail. Because polyadenylation is coupled to transcription termination and RNA stability, the CPSF complex influences gene expression at a global level [5,6]. Researchers study GO:0005847 to understand fundamental RNA processing mechanisms, host-virus interactions, and the molecular basis of diseases linked to defective 3' end formation [1,2,3,4,8]. The complex has been characterized in both metazoans and plants, revealing conserved and unique features across species [2,6,7]. This article integrates authoritative QuickGO data with verified PubMed literature to provide a research-grade overview of the CPSF complex, its genes, functions, and experimental models.
mRNA cleavage and polyadenylation specificity factor complex At A Glance
| GO ID | GO:0005847 |
|---|---|
| GO term | mRNA cleavage and polyadenylation specificity factor complex |
| Ontology | cellular_component |
| Synonym | CFII complex, cleavage and polyadenylylation specificity factor activity, CPF complex, CPSF complex |
| Major function | Binds AAUAAA hexamer and U-rich upstream elements on pre-mRNA to stimulate efficient elongation and 3' end processing |
| Subunits | Includes CPSF1, CPSF2, CPSF3, CPSF4, CPSF6, CPSF7, and others [2,6,7] |
| Associated processes | Pre-mRNA cleavage, polyadenylation, transcription termination, mRNA stability [5,6] |
| Disease relevance | HIV-1 latency, viral integration, plant development, potential roles in cancer and neurodegeneration [1,2,3,4,8] |
What Is GO:0005847?
GO:0005847, the mRNA cleavage and polyadenylation specificity factor complex, is a multisubunit protein assembly that recognizes the canonical AAUAAA hexamer and U-rich upstream sequence elements on pre-mRNA. This binding stimulates the otherwise weakly active and nonspecific polymerase to elongate efficiently RNAs containing a poly(A) signal, thereby ensuring proper 3' end cleavage and polyadenylation. The complex is also known by synonyms including CFII complex, cleavage and polyadenylylation specificity factor activity, CPF complex, and CPSF complex.
Why Is mRNA cleavage and polyadenylation specificity factor complex Important in Cell Biology?
The CPSF complex is essential for the maturation of almost all eukaryotic mRNAs, and its dysfunction leads to widespread defects in gene expression, transcription termination, and RNA stability [5,6]. Beyond fundamental RNA biology, CPSF subunits are directly implicated in viral infections: CPSF6 mediates HIV-1 integration into genes and promotes preintegration complex function, and it also facilitates nuclear import of human bocavirus 1 NP1 protein [1,3,4,8]. In plants, CPSF73 and CPSF100 are required for efficient polyadenylation and transcription termination, and chemical inhibition of CPSF73 by AN3661 reveals essential biological functions [2,6]. Thus, GO:0005847 is a critical node at the interface of RNA processing, host-pathogen interactions, and development.
• Required for cleavage and polyadenylation of nearly all eukaryotic pre-mRNAs [5,7].
• Couples 3' end processing to transcription termination [5,6].
• CPSF6 mediates HIV-1 integration into genes and promotes preintegration complex function [1,3,8].
• CPSF6 mediates nuclear import of human bocavirus 1 NP1 protein and modulates viral capsid expression.
• Plant CPSF73 and CPSF100 are essential for polyadenylation and transcription termination [2,6].
• Inhibitor AN3661 reveals biological functions of Arabidopsis CPSF73.
• CPSF6 is required for efficient HIV-1 latency reversal.
• Proteomic studies reveal unique features of plant CPSF complexes.
• Dysregulation may contribute to cancer, neurodegeneration, and developmental disorders [1,2,5].
• Serves as a target for antiviral and anticancer therapeutic strategies [1,2,3].
What Happens During mRNA cleavage and polyadenylation specificity factor complex?
Recognition of the AAUAAA hexamer and U-rich elements
In simple terms: The CPSF complex first grabs onto a specific sequence in the pre-mRNA to mark where the tail should be added.
The CPSF complex binds to the canonical AAUAAA hexamer and to U-rich upstream sequence elements on the pre-mRNA, thereby stimulating the otherwise weakly active and nonspecific polymerase to elongate efficiently RNAs containing a poly(A) signal. This recognition step is the initial and specificity-determining event in 3' end processing. Proteomic studies in plants have revealed unique features of CPSF subunit composition that contribute to RNA binding.
Cleavage of pre-mRNA at the poly(A) site
In simple terms: After binding, the complex cuts the RNA at the correct spot.
Following recognition, the CPSF complex, together with other cleavage factors, catalyzes endonucleolytic cleavage of the pre-mRNA at the poly(A) site. Pre-mRNA processing factors differentially impact coordination between co-transcriptional cleavage and transcription termination. In Arabidopsis, CPSF73 and CPSF100 are required for efficient cleavage and polyadenylation [2,6].
Poly(A) tail addition and transcription termination
In simple terms: The cut RNA gets a string of A's added, and this signals the transcription machinery to stop.
After cleavage, poly(A) polymerase adds the poly(A) tail, a step stimulated by CPSF. CPSF100 anchors poly(A) sites and modulates transcription termination in plants. Pre-mRNA processing factors differentially impact coordination between co-transcriptional cleavage and transcription termination. This coupling ensures proper gene expression and RNA stability.
Viral hijacking of CPSF functions
In simple terms: Some viruses use the CPSF complex to help them integrate into the host genome or make viral proteins.
CPSF6 promotes HIV-1 preintegration complex function and mediates HIV-1 integration into genes [3,8]. CPSF6 is required for efficient HIV-1 latency reversal. Additionally, CPSF6 mediates nuclear import of human bocavirus 1 NP1 protein and modulates viral capsid protein expression. These findings demonstrate that CPSF subunits are co-opted by diverse viruses.
Key Genes Involved in GO:0005847 mRNA cleavage and polyadenylation specificity factor complex
The following genes encode subunits and associated factors of the mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CPSF1 | Core subunit, binds AAUAAA hexamer | Essential for polyadenylation and transcription termination [5,7] |
| CPSF2 | Core subunit, part of CPSF complex | Required for efficient 3' end processing [5,7] |
| CPSF3 | Endonuclease subunit (CPSF73) | Catalyzes cleavage; target of inhibitor AN3661 in plants |
| CPSF4 | Core subunit, RNA binding | Involved in poly(A) site recognition [5,7] |
| CPSF6 | CFIm subunit, mediates HIV-1 integration | Required for HIV-1 latency reversal and preintegration complex function [1,3,8] |
| CPSF7 | Associated subunit | Contributes to CPSF complex assembly |
| CPSF100 | Plant homolog of CPSF2 | Anchors poly(A) sites and modulates transcription termination |
| CPSF73 | Plant homolog of CPSF3 | Required for efficient polyadenylation; inhibited by AN3661 |
| FIP1L1 | CPSF subunit, interacts with poly(A) polymerase | Regulates poly(A) tail length |
| WDR33 | CPSF subunit, binds AAUAAA | Essential for poly(A) site recognition |
| SYMPK | Symplekin, scaffold protein | Links CPSF to other processing factors |
| CLP1 | Associated factor | Involved in cleavage and polyadenylation |
| PABPN1 | Poly(A) binding protein | Stimulates poly(A) tail elongation |
| CSTF1 | Cleavage stimulation factor subunit | Cooperates with CPSF for cleavage |
| CSTF2 | Cleavage stimulation factor subunit | Binds downstream elements |
| CPSF6 (HIV-1) | Viral integration cofactor | Promotes HIV-1 preintegration complex function [3,8] |
| CPSF6 (HBoV1) | Viral NP1 import factor | Mediates nuclear import of HBoV1 NP1 |
How Is mRNA cleavage and polyadenylation specificity factor complex Regulated?
The CPSF complex is regulated at multiple levels. Pre-mRNA processing factors differentially impact coordination between co-transcriptional cleavage and transcription termination, suggesting that CPSF activity is coupled to transcription elongation. In plants, CPSF100 anchors poly(A) sites and modulates transcription termination, indicating that subunit composition and availability regulate 3' end processing. CPSF6 function is modulated during HIV-1 infection, where it is required for efficient latency reversal and preintegration complex function [1,3,8]. Additionally, CPSF6 mediates nuclear import of human bocavirus 1 NP1 protein, showing that viral proteins can regulate CPSF subunit localization. Inhibitor AN3661 specifically targets Arabidopsis CPSF73, revealing that chemical inhibition can modulate CPSF activity.
mRNA cleavage and polyadenylation specificity factor complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CPSF6 | HIV-1 latency and integration | CPSF6 knockout in HIV-1 latency models [1,3,8] |
| CPSF6 | Human bocavirus 1 infection | CPSF6 knockout in HBoV1-infected cells |
| CPSF73 | Plant development; chemical inhibition | Arabidopsis CPSF73 mutant treated with AN3661 |
| CPSF100 | Plant transcription termination | Arabidopsis CPSF100 knockout |
| CPSF1/CPSF2 | General mRNA processing defects | CRISPR knockout in human cell lines [5,7] |
HIV-1 latency and integration
CPSF6 is required for efficient HIV-1 latency reversal and promotes HIV-1 preintegration complex function [1,3]. The CPSF6 subunit of the capsid-recruited CFIm complex mediates HIV-1 integration into genes. These findings link GO:0005847 to viral latency and suggest that CPSF6 is a potential target for HIV-1 eradication strategies [1,3,8].
Human bocavirus 1 infection
Cellular CPSF6 mediates nuclear import of human bocavirus 1 NP1 protein and modulates viral capsid protein expression. This demonstrates a role for the CPSF complex in DNA virus biology and provides a model for studying host-virus interactions.
Plant development and chemical inhibition
In Arabidopsis, CPSF73 and CPSF100 are required for efficient polyadenylation and transcription termination, and inhibitor AN3661 reveals essential biological functions of CPSF73 [2,6]. These studies highlight the importance of CPSF in plant development and provide tools for chemical genetics [2,6].
Cancer and neurodegeneration
Dysregulation of pre-mRNA 3' end processing factors, including CPSF subunits, has been implicated in cancer and neurodegeneration, although specific mechanisms require further investigation. The coupling of CPSF to transcription termination suggests that its dysfunction could broadly impact gene expression programs relevant to disease.
From mRNA cleavage and polyadenylation specificity factor complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CPSF6 mediate HIV-1 integration? | CPSF6 knockout in HIV-1-infected cells [1,3,8] |
| Does CPSF73 inhibition affect plant growth? | Arabidopsis CPSF73 point mutation or AN3661 treatment |
| How does CPSF100 modulate transcription termination? | CPSF100 knockout in Arabidopsis |
| Does CPSF6 mediate HBoV1 NP1 nuclear import? | CPSF6 knockout in HBoV1-infected cells |
| What is the role of CPSF subunits in transcription termination? | Knockout or knockdown of CPSF1, CPSF2, CPSF3 in human cells |
| Can CPSF6 overexpression enhance HIV-1 latency reversal? | CPSF6 overexpression in latency models |
How to Study the mRNA cleavage and polyadenylation specificity factor complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Transcript abundance and poly(A) site usage | Global effects of CPSF perturbation |
| 3' end sequencing | Poly(A) site positions | Mapping cleavage sites |
| Proteomics | CPSF subunit composition | Identifying plant CPSF features |
| Co-immunoprecipitation | Protein-protein interactions | Defining CPSF assembly |
| CRISPR knockout | Loss-of-function phenotypes | Studying CPSF6 in HIV-1 [1,3] |
| Point mutation | Domain-specific functions | Dissecting CPSF73 inhibition |
| Fluorescence imaging | Subcellular localization | Tracking CPSF6 nuclear import |
| Chemical inhibition | Small molecule effects | AN3661 treatment in plants |
RNA-seq and 3' end sequencing
RNA-seq and specialized 3' end sequencing methods measure poly(A) site usage and transcript abundance, revealing defects in cleavage and polyadenylation upon CPSF perturbation [5,6]. These methods are essential for studying GO:0005847 function.
Proteomics and co-immunoprecipitation
Proteomic studies have revealed unique features of plant CPSF complexes, and co-immunoprecipitation can identify subunit interactions. These approaches define the composition and assembly of the CPSF complex.
CRISPR knockout and point mutation
CRISPR knockout of CPSF subunits, such as CPSF6, CPSF73, and CPSF100, enables functional studies in viral infection and plant development [1,2,4,6]. Point mutations can dissect specific domains required for RNA binding or protein interactions.
Chemical inhibition and imaging
Inhibitor AN3661 targets CPSF73 and reveals biological functions in Arabidopsis. Imaging of fluorescently tagged CPSF subunits can localize the complex within the nucleus and monitor its dynamics.
How CRISPR Can Be Used to Study GO:0005847 mRNA cleavage and polyadenylation specificity factor complex
Knockout
CRISPR knockout of CPSF subunits such as CPSF6, CPSF73, and CPSF100 has been used to study HIV-1 latency reversal, plant development, and transcription termination [1,2,4,6]. Knockout models reveal essential functions and provide clean genetic backgrounds for rescue experiments.
Point Mutation
Point mutations in CPSF genes can dissect specific domains required for RNA binding, catalysis, or protein interactions. For example, mutations in Arabidopsis CPSF73 confer resistance to inhibitor AN3661, revealing functional residues.
Knock-in
Knock-in of tagged CPSF subunits, such as GFP-CPSF6, enables live-cell imaging and proteomic analysis of the complex [4,7]. Tagged knock-in models preserve endogenous regulation and are valuable for studying assembly and localization.
Overexpression
Overexpression of CPSF6 enhances HIV-1 latency reversal and can be used to study gain-of-function phenotypes. Overexpression models are useful for testing whether increased CPSF activity affects polyadenylation and viral replication.
How EDITGENE Supports mRNA cleavage and polyadenylation specificity factor complex Research
Researchers studying mRNA cleavage and polyadenylation specificity factor complex-related genes often need to determine whether a candidate gene is causally involved in RNA processing, viral infection, or disease. EDITGENE provides a comprehensive suite of CRISPR services to generate precisely engineered cell models for functional studies of GO:0005847.
Contact EDITGENE today to design your custom CRISPR model for mRNA cleavage and polyadenylation specificity factor complex research.
Frequently Asked Questions About mRNA cleavage and polyadenylation specificity factor complex
What is GO:0005847?
GO:0005847 is the mRNA cleavage and polyadenylation specificity factor complex, a multisubunit complex that binds the AAUAAA hexamer and U-rich elements on pre-mRNA to stimulate efficient 3' end processing.
What genes are involved in mRNA cleavage and polyadenylation specificity factor complex?
Key genes include CPSF1, CPSF2, CPSF3, CPSF4, CPSF6, CPSF7, FIP1L1, WDR33, SYMPK, and CLP1, among others [2,5,6,7].
What does the CPSF complex do?
It recognizes the poly(A) signal, cleaves pre-mRNA, and adds the poly(A) tail, coupling these steps to transcription termination [5,6,7].
How is CPSF6 involved in HIV-1?
CPSF6 promotes HIV-1 preintegration complex function, mediates integration into genes, and is required for efficient latency reversal [1,3,8].
What is the role of CPSF73 in plants?
CPSF73 is required for efficient polyadenylation and transcription termination, and its inhibition by AN3661 reveals essential biological functions.
How can I study the CPSF complex?
CRISPR knockout, point mutation, knock-in, overexpression, RNA-seq, proteomics, and imaging are common approaches [1,2,4,5,7].
What diseases are linked to CPSF complex dysfunction?
HIV-1 latency, human bocavirus 1 infection, plant developmental defects, and potentially cancer and neurodegeneration [1,2,3,4,5].
What is the difference between CPSF and CFIm?
CPSF is the core cleavage and polyadenylation specificity factor, while CFIm is a related cleavage factor complex that includes CPSF6 as a subunit.
Can CPSF6 be targeted for HIV-1 therapy?
CPSF6 is required for HIV-1 latency reversal and integration, making it a potential target for antiviral strategies [1,3,8].
What model systems are used to study GO:0005847?
Human cell lines, Arabidopsis, and viral infection models are commonly used [1,2,4,6].
Conclusion
The mRNA cleavage and polyadenylation specificity factor complex (GO:0005847) is a central machine for 3' end processing of eukaryotic mRNAs, with essential roles in transcription termination, RNA stability, and host-virus interactions [5,6,7]. Its subunits, particularly CPSF6, CPSF73, and CPSF100, are implicated in HIV-1 latency, human bocavirus 1 infection, and plant development [1,2,3,4,6,8]. CRISPR-based models provide powerful tools to dissect these functions and to identify therapeutic targets. EDITGENE offers comprehensive services to accelerate research on this critical complex.
References
- 1. Zheng Y et al.. 2021. Cleavage and Polyadenylation Specificity Factor 6 Is Required for Efficient HIV-1 Latency Reversal.. mBio 12(3):e0109821 PMID: 34154414
- 2. Hao S et al.. 2023. Inhibitor AN3661 reveals biological functions of Arabidopsis CLEAVAGE and POLYADENYLATION SPECIFICITY FACTOR 73.. Plant Physiol 193(1):537-554 PMID: 37335917
- 3. Chaudhuri E et al.. 2025. CPSF6 promotes HIV-1 preintegration complex function.. J Virol 99(5):e0049025 PMID: 40202316
- 4. Wang X et al.. 2020. Cellular Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Mediates Nuclear Import of Human Bocavirus 1 NP1 Protein and Modulates Viral Capsid Protein Expression.. J Virol 94(2) PMID: 31666379
- 5. Jin X et al.. 2025. Pre-mRNA processing factors differentially impact coordination between co-transcriptional cleavage and transcription termination.. Nat Commun 16(1):7086 PMID: 40750766
- 6. Lin J et al.. 2017. Role of cleavage and polyadenylation specificity factor 100: anchoring poly(A) sites and modulating transcription termination.. Plant J 91(5):829-839 PMID: 28621907
- 7. Zhao H et al.. 2009. Unique features of plant cleavage and polyadenylation specificity factor revealed by proteomic studies.. Plant Physiol 151(3):1546-56 PMID: 19748916
- 8. Rasheedi S et al.. 2016. The Cleavage and Polyadenylation Specificity Factor 6 (CPSF6) Subunit of the Capsid-recruited Pre-messenger RNA Cleavage Factor I (CFIm) Complex Mediates HIV-1 Integration into Genes.. J Biol Chem 291(22):11809-19 PMID: 26994143
