GO:1990726 Lsm1-7-Pat1 complex: mRNA Decay and Viral Replication, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1990726 (Lsm1-7-Pat1 complex) is a conserved eukaryotic cytoplasmic complex that links 3' deadenylation to 5' decapping during mRNA turnover.
• The complex is composed of the Lsm1-7 heptameric ring and the Pat1 protein, which together bind RNA and activate the decapping enzyme Dcp1/Dcp2.
• Lsm1-7-Pat1 binds to stress-activated mRNAs and modulates the cellular response to hyperosmotic shock.
• The complex promotes viral RNA translation and replication by differential mechanisms, highlighting its role in host-pathogen interactions.
• Both the Sm-domain and C-terminal extension of Lsm1 are important for RNA binding, and Pat1 contributes to the RNA-binding activity of the complex.
• Dysregulation of Lsm1-7-Pat1 components is implicated in cancer and other diseases, making it a potential therapeutic target.
Description
The Lsm1-7-Pat1 complex (GO:1990726) is a conserved eukaryotic cytoplasmic complex that plays a central role in mRNA decay and translational control. It is composed of the Lsm1-7 heptameric ring and the Pat1 protein, which together coordinate the removal of the 5' cap after deadenylation, thereby linking 3' and 5' ends in mRNA turnover. This complex is essential for the degradation of a subset of mRNAs and for the cellular response to stress. Understanding its function is critical for researchers studying post-transcriptional gene regulation, viral replication, and disease mechanisms. The complex has been implicated in hyperosmotic shock response, viral RNA translation, and cancer biology, making it a subject of intense investigation. Its architecture and RNA-binding properties have been elucidated through structural and biochemical studies, providing a framework for functional studies.
Lsm1-7-Pat1 complex At A Glance
| GO ID | GO:1990726 |
|---|---|
| GO term | Lsm1-7-Pat1 complex |
| Ontology | biological_process |
| Synonym | None |
| Major function | mRNA decapping activation and translational control |
| Components | Lsm1, Lsm2, Lsm3, Lsm4, Lsm5, Lsm6, Lsm7, Pat1 |
| Cellular location | Cytoplasm |
| Associated processes | mRNA decay, stress response, viral replication |
What Is GO:1990726?
The Lsm1-7-Pat1 complex is a cytoplasmic protein complex that consists of the Lsm1-7 ring and the Pat1 protein. It functions in mRNA decay by promoting decapping after deadenylation, and it also modulates the translation and stability of specific mRNAs, particularly under stress conditions. The complex binds RNA and facilitates the activation of the decapping enzyme Dcp1/Dcp2, thereby linking 3' deadenylation to 5' decapping.
Why Is Lsm1-7-Pat1 complex Important in Cell Biology?
The Lsm1-7-Pat1 complex is a key regulator of mRNA stability and translation, influencing gene expression programs essential for cell growth, stress responses, and viral infections. Its dysfunction has been linked to cancer and other diseases, and it serves as a model for understanding the coupling of deadenylation and decapping.
• Regulates mRNA decay by linking 3' deadenylation to 5' decapping.
• Modulates the cellular response to hyperosmotic stress.
• Promotes viral RNA translation and replication.
• Involved in the degradation of stress-activated mRNAs.
• Its RNA-binding activity is essential for decapping activation.
• Implicated in cancer and other human diseases.
• Provides a paradigm for understanding mRNA turnover mechanisms.
• Potential target for antiviral and anticancer therapies.
What Happens During Lsm1-7-Pat1 complex?
Recognition and Binding of mRNA
In simple terms: The complex grabs onto the mRNA tail after it has been shortened.
The Lsm1-7-Pat1 complex binds to the 3' end of deadenylated mRNAs. Both the Sm-domain and C-terminal extension of Lsm1 are important for RNA binding, and Pat1 contributes to the RNA-binding activity of the complex. This binding is a prerequisite for subsequent decapping activation.
Activation of Decapping
In simple terms: The complex helps remove the protective cap from the mRNA, marking it for destruction.
After binding to mRNA, the Lsm1-7-Pat1 complex facilitates the activation of the decapping enzyme Dcp1/Dcp2. Lsm2 and Lsm3 bridge the interaction of the Lsm1-7 complex with Pat1 for decapping activation. The complex enhances the post-binding steps of decapping, leading to cap removal.
mRNA Degradation
In simple terms: Once the cap is removed, the mRNA is quickly degraded.
Following decapping, the mRNA is degraded by Xrn1 from the 5' end. The Lsm1-7-Pat1 complex thus links 3' deadenylation to 5' decapping, ensuring efficient mRNA turnover.
Stress Response and Translational Control
In simple terms: Under stress, the complex helps decide which mRNAs are translated or destroyed.
The Lsm1-7-Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock. It also promotes viral RNA translation and replication by differential mechanisms, indicating a broader role in translational control.
Key Genes Involved in GO:1990726 Lsm1-7-Pat1 complex
The Lsm1-7-Pat1 complex comprises eight core proteins, each with distinct roles in RNA binding, complex assembly, and decapping activation.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Lsm1 | RNA binding, complex assembly | Essential for decapping activation |
| Lsm2 | Bridges Lsm1-7 with Pat1 | Required for decapping activation |
| Lsm3 | Bridges Lsm1-7 with Pat1 | Required for decapping activation |
| Lsm4 | Structural component of Lsm ring | Conserved in mRNA decay |
| Lsm5 | Structural component of Lsm ring | Conserved in mRNA decay |
| Lsm6 | Structural component of Lsm ring | Conserved in mRNA decay |
| Lsm7 | Structural component of Lsm ring | Conserved in mRNA decay |
| Pat1 | RNA binding, decapping activation | Contributes to RNA binding |
| Dcp1 | Decapping enzyme subunit | Target of Lsm1-7-Pat1 activation |
| Dcp2 | Decapping enzyme catalytic subunit | Target of Lsm1-7-Pat1 activation |
| Xrn1 | 5' to 3' exonuclease | Degrades decapped mRNA |
| Lsm1-7 complex | Heptameric ring | Core of the complex |
| Pat1 | Enhances RNA binding | Modulates complex activity |
| Lsm1 C-terminal extension | RNA binding | Important for function |
| Lsm1 Sm-domain | RNA binding | Important for function |
| Lsm2-3 | Interaction with Pat1 | Bridge for decapping |
| Lsm1-7-Pat1 complex | mRNA decay and translation | Central to post-transcriptional regulation |
How Is Lsm1-7-Pat1 complex Regulated?
The Lsm1-7-Pat1 complex is regulated at multiple levels. Its activity is modulated by stress conditions, such as hyperosmotic shock, which affects its binding to specific mRNAs. The complex interacts with decapping factors and is influenced by the deadenylation machinery. Additionally, viral proteins can hijack the complex to promote viral RNA translation and replication.
Lsm1-7-Pat1 complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Lsm1 | Cancer | Knockout cell lines |
| Pat1 | Cancer | Overexpression models |
| Lsm1-7-Pat1 complex | Viral infection | Viral replication assays |
| Lsm2 | Cancer | Point mutation models |
| Lsm3 | Cancer | Knock-in models |
Cancer
Dysregulation of mRNA decay factors, including Lsm1-7-Pat1 components, has been implicated in cancer. Altered expression of Lsm1 and Pat1 may contribute to tumorigenesis by stabilizing oncogenic mRNAs.
Viral Infections
The Lsm1-7-Pat1 complex promotes viral RNA translation and replication, making it a potential host factor for antiviral therapy.
Neurodegeneration
Defects in mRNA decay pathways, including those involving Lsm1-7-Pat1, have been linked to neurodegenerative diseases, although direct evidence is still emerging.
From Lsm1-7-Pat1 complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does Lsm1 loss affect mRNA stability? | Lsm1 knockout cell line |
| Does Pat1 mutation alter RNA binding? | Pat1 point mutation knock-in |
| Can Lsm1-7-Pat1 be tagged for imaging? | Tagged knock-in of Lsm1 |
| Does overexpression of Pat1 affect viral replication? | Pat1 overexpression cell line |
| What mRNAs are bound by the complex? | CLIP-seq with tagged Lsm1 |
| Does Lsm2 mutation affect decapping? | Lsm2 point mutation |
How to Study the Lsm1-7-Pat1 complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RIP-seq | mRNA binding | Identify target mRNAs |
| In vitro decapping | Decapping activity | Assess activation |
| Crystallography | Structure | Determine architecture |
| Viral replication assay | Viral RNA replication | Test proviral role |
| Western blot | Protein levels | Check expression |
| qRT-PCR | mRNA levels | Measure stability |
| CLIP | RNA binding sites | Map interactions |
| Knockdown | Loss of function | Phenotypic analysis |
RNA Immunoprecipitation (RIP)
RIP followed by sequencing can identify mRNAs bound by the Lsm1-7-Pat1 complex. This method has been used to show binding to stress-activated mRNAs.
In vitro decapping assays
Decapping activity can be measured using purified components to assess the role of Lsm1-7-Pat1 in activating Dcp1/Dcp2.
Structural biology
Crystal structures of the Lsm1-7-Pat1 complex have revealed its architecture and RNA-binding interfaces.
Viral replication assays
The effect of Lsm1-7-Pat1 on viral RNA translation and replication can be tested using viral infection models.
How CRISPR Can Be Used to Study GO:1990726 Lsm1-7-Pat1 complex
Knockout
CRISPR knockout of Lsm1 or Pat1 can abolish complex function, leading to mRNA decay defects and altered stress responses.
Point Mutation
Point mutations in the RNA-binding domains of Lsm1 or Pat1 can dissect their specific contributions to complex activity.
Knock-in
Knock-in of tagged versions of Lsm1 or Pat1 allows for imaging and proteomic studies of the complex.
Overexpression
Overexpression of Pat1 or Lsm1 can enhance decapping activity and affect viral replication, providing gain-of-function models.
How EDITGENE Supports Lsm1-7-Pat1 complex Research
Researchers studying Lsm1-7-Pat1 complex-related genes often need to determine whether a candidate gene is causally involved in mRNA decay, stress response, or viral replication. EDITGENE provides custom CRISPR services to create precisely engineered cell models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for Lsm1-7-Pat1 complex research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| LSM1 Knockout HEK293 Cell Line | EDJ-KQ8734 | Human | 27257 | Details Get a Quote |
| LSM1 Knockout HCT 116 Cell Line | EDJ-KQ34976 | Human | 27257 | Details Get a Quote |
| LSM1 Knockout HeLa Cell Line | EDJ-KQ34977 | Human | 27257 | Details Get a Quote |
| LSM1 Knockout A-549 Cell Line | EDJ-KQ33711 | Human | 27257 | Details Get a Quote |
| LSM5 Knockout HEK293 Cell Line | EDJ-KQ51126 | Human | 23658 | Details Get a Quote |
| LSM3 Knockout HEK293 Cell Line | EDJ-KQ51211 | Human | 27258 | Details Get a Quote |
| LSM5 Knockout HeLa Cell Line | EDJ-KQ55792 | Human | 23658 | Details Get a Quote |
| LSM3 Knockout HeLa Cell Line | EDJ-KQ56042 | Human | 27258 | Details Get a Quote |
| LSM5 Knockout A-549 Cell Line | EDJ-KQ64288 | Human | 23658 | Details Get a Quote |
| LSM3 Knockout A-549 Cell Line | EDJ-KQ64528 | Human | 27258 | Details Get a Quote |
| LSM5 Knockout HCT 116 Cell Line | EDJ-KQ72736 | Human | 23658 | Details Get a Quote |
| LSM3 Knockout HCT 116 Cell Line | EDJ-KQ72987 | Human | 27258 | Details Get a Quote |
Frequently Asked Questions About Lsm1-7-Pat1 complex
What is the Lsm1-7-Pat1 complex?
It is a conserved eukaryotic complex that links mRNA deadenylation to decapping, composed of Lsm1-7 and Pat1.
What genes are involved in the Lsm1-7-Pat1 complex?
The complex includes Lsm1, Lsm2, Lsm3, Lsm4, Lsm5, Lsm6, Lsm7, and Pat1.
What is the function of GO:1990726?
GO:1990726 describes the biological process of mRNA decapping activation and translational control mediated by the Lsm1-7-Pat1 complex.
How does Lsm1-7-Pat1 activate decapping?
It binds to deadenylated mRNA and facilitates the activation of Dcp1/Dcp2, leading to cap removal.
Is Lsm1-7-Pat1 involved in disease?
Yes, it has been implicated in cancer and viral infections.
What is the role of Pat1 in the complex?
Pat1 contributes to RNA binding and is essential for decapping activation.
How is the Lsm1-7-Pat1 complex regulated?
It is regulated by stress conditions and interactions with other decay factors.
What methods are used to study Lsm1-7-Pat1?
Common methods include RIP-seq, in vitro decapping assays, and structural biology.
Can CRISPR be used to study Lsm1-7-Pat1?
Yes, knockout, point mutation, and knock-in models can be generated to study its function.
What are the key takeaways about Lsm1-7-Pat1?
It is a central mRNA decay factor with roles in stress response, viral replication, and disease.
Conclusion
The Lsm1-7-Pat1 complex (GO:1990726) is a critical regulator of mRNA turnover and translation, with far-reaching implications for cellular stress responses, viral infections, and cancer. Its conserved architecture and mechanism of action provide a paradigm for understanding post-transcriptional gene regulation. Continued research using advanced CRISPR models will further elucidate its roles in health and disease.
References
- 1. Garre E et al.. 2018. The Lsm1-7/Pat1 complex binds to stress-activated mRNAs and modulates the response to hyperosmotic shock.. PLoS Genet 14(7):e1007563 PMID: 30059503
- 2. Sharif H et al.. 2013. Architecture of the Lsm1-7-Pat1 complex: a conserved assembly in eukaryotic mRNA turnover.. Cell Rep 5(2):283-91 PMID: 24139796
- 3. Jungfleisch J et al.. 2015. The Lsm1-7-Pat1 complex promotes viral RNA translation and replication by differential mechanisms.. RNA 21(8):1469-79 PMID: 26092942
- 4. Chowdhury A et al.. 2014. Pat1 contributes to the RNA binding activity of the Lsm1-7-Pat1 complex.. RNA 20(9):1465-75 PMID: 25035297
- 5. Wu D et al.. 2014. Lsm2 and Lsm3 bridge the interaction of the Lsm1-7 complex with Pat1 for decapping activation.. Cell Res 24(2):233-46 PMID: 24247251
- 6. Chowdhury A et al.. 2012. Both Sm-domain and C-terminal extension of Lsm1 are important for the RNA-binding activity of the Lsm1-7-Pat1 complex.. RNA 18(5):936-44 PMID: 22450758
- 7. Tharun S. 2009. Lsm1-7-Pat1 complex: a link between 3' and 5'-ends in mRNA decay?. RNA Biol 6(3):228-32 PMID: 19279404
- 8. Chowdhury A et al.. 2009. Activation of decapping involves binding of the mRNA and facilitation of the post-binding steps by the Lsm1-7-Pat1 complex.. RNA 15(10):1837-48 PMID: 19643916
