GO:1904803 regulation of translation involved in cellular response to UV: Protein Synthesis Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1904803 describes how cells adjust protein synthesis specifically when exposed to ultraviolet (UV) light, a key part of the UV stress response.
• UV radiation damages DNA and RNA, triggering a rapid but temporary shutdown of global translation to conserve energy and prioritize repair.
• This regulation involves phosphorylation of eIF2α by stress kinases like GCN2, which reduces cap-dependent translation initiation.
• RNA-binding proteins such as CIRBP are induced by UV and can modulate translation of specific mRNAs, contributing to cell survival.
• Dysregulation of UV-responsive translation is linked to cancer, neurodegeneration, and impaired tissue homeostasis.
• Studying GO:1904803 requires methods like Ribo-seq, polysome profiling, and CRISPR-based gene editing to dissect causal roles.
Description
Ultraviolet (UV) radiation is a ubiquitous environmental stressor that damages DNA and RNA, and cells have evolved complex programs to survive and repair this damage. One critical component of the cellular response to UV is the regulation of translation, the process by which mRNAs are decoded into proteins. The Gene Ontology term GO:1904803, regulation of translation involved in cellular response to UV, captures any regulatory event that modulates translation specifically as part of the UV stress response. This term is essential for researchers studying how cells balance protein synthesis with damage repair, and how failures in this balance contribute to diseases such as cancer and neurodegeneration. Understanding GO:1904803 provides a framework for dissecting the molecular mechanisms that link UV exposure to changes in the proteome and cell fate.
regulation of translation involved in cellular response to UV At A Glance
| GO ID | GO:1904803 |
|---|---|
| GO term | regulation of translation involved in cellular response to UV |
| Ontology | biological_process |
| Synonym | regulation of protein synthesis involved in cellular response to UV; regulation of translation involved in cellular response to ultraviolet light stimulus; regulation of translation involved in cellular response to UV radiation stimulus |
| Major function | Modulates protein synthesis to promote cell survival and DNA repair after UV damage |
| Related processes | DNA damage response, integrated stress response, autophagy, apoptosis |
| Key regulators | eIF2α kinases (GCN2, PERK), RNA-binding proteins (CIRBP), E2F1 |
| Disease relevance | Cancer, neurodegeneration, UV-sensitive syndromes |
What Is GO:1904803?
GO:1904803 is defined as any regulation of translation that is involved in cellular response to UV. In other words, it encompasses all processes that control the rate, fidelity, or specificity of protein synthesis when a cell is exposed to ultraviolet light. This includes both global translational reprogramming and mRNA-specific translational control that occurs as part of the UV stress response.
Why Is regulation of translation involved in cellular response to UV Important in Cell Biology?
Regulation of translation during the UV response is vital because it allows cells to rapidly reprogram gene expression without waiting for new transcription, which is especially important when UV damages DNA and impairs RNA polymerase II activity. By temporarily halting global protein synthesis and selectively translating repair factors or survival proteins, cells can mitigate UV-induced damage and avoid apoptosis. Dysregulation of this process is implicated in cancer progression, where cancer cells may hijack translational control to survive genotoxic stress, and in neurodegenerative diseases where chronic stress responses contribute to neuronal loss.
• Enables rapid proteome remodeling independent of new transcription, crucial when UV damages DNA.
• Conserves energy and resources by temporarily reducing global translation during stress.
• Facilitates selective translation of DNA repair proteins and stress-response factors.
• Prevents accumulation of damaged or misfolded proteins after UV exposure.
• Modulates cell fate decisions between survival, senescence, and apoptosis.
• Contributes to skin cancer development when misregulated.
• Plays a role in UV-induced inflammation and immune responses.
• Provides targets for therapeutic intervention in UV-related pathologies.
• Helps maintain stem cell function and tissue homeostasis after UV damage.
• Is a paradigm for understanding stress-induced translational control in general.
What Happens During regulation of translation involved in cellular response to UV?
UV-induced stress sensing and eIF2α phosphorylation
In simple terms: When UV light hits a cell, it triggers a stress alarm that puts the brakes on general protein production.
UV radiation causes DNA damage and activates stress kinases such as GCN2, which phosphorylate the translation initiation factor eIF2α. This phosphorylation inhibits the recycling of eIF2-GTP, leading to a global reduction in cap-dependent translation initiation. This step is a hallmark of the integrated stress response and is critical for redirecting resources toward repair and survival.
Global translational repression and polysome disassembly
In simple terms: The cell's protein factories, ribosomes, stop working on most mRNAs to save energy.
Following eIF2α phosphorylation, global translation is rapidly downregulated, and polysomes disassemble. This repression is transient and reversible, allowing cells to resume protein synthesis once damage is repaired. The shutdown also prevents translation of aberrant proteins from damaged mRNAs.
Selective translation of stress-responsive mRNAs
In simple terms: While most protein production stops, a few key proteins that help the cell survive are still made.
Certain mRNAs, such as those encoding transcription factors like ATF4 or RNA-binding proteins like CIRBP, contain upstream open reading frames or internal ribosome entry sites that allow their translation despite global repression. CIRBP is induced by UV and can modulate the translation of specific targets to promote survival. This selective translation is essential for mounting an effective UV response.
RNA polymerase II regulation and transcription-translation coupling
In simple terms: UV damage also affects the enzyme that makes mRNA, and the cell coordinates this with translation.
UV-induced DNA damage stalls RNA polymerase II (RNAPII), and the regulation of the RNAPII pool is integral to the DNA damage response. This coupling ensures that translation is adjusted in accordance with transcriptional capacity, preventing proteotoxic stress. E2F1 also plays a role in coordinating DNA damage responses with translational programs.
Recovery and translational restart
In simple terms: Once the damage is fixed, the cell restarts normal protein production.
After DNA repair, eIF2α is dephosphorylated, and translation resumes. This recovery phase is critical for restoring cellular functions and preventing chronic stress that could lead to apoptosis or senescence. Dysregulation of this restart can contribute to cancer and aging.
Key Genes Involved in GO:1904803 regulation of translation involved in cellular response to UV
The following genes and proteins are central to the regulation of translation during the cellular response to UV, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| EIF2S1 | Encodes eIF2α; phosphorylation inhibits global translation | Key node in integrated stress response; target for modulating UV sensitivity |
| GCN2 (EIF2AK4) | Kinase that phosphorylates eIF2α upon UV stress | Mediates translational repression; knockout models show altered UV survival |
| PERK (EIF2AK3) | ER stress kinase that also phosphorylates eIF2α | Cross-talk with UV response; potential therapeutic target |
| CIRBP | Cold-inducible RNA-binding protein; modulates translation of specific mRNAs | UV-induced; promotes cell survival; biomarker of stress |
| E2F1 | Transcription factor with nontranscriptional roles in DNA damage response | Regulates translation-related genes; links cell cycle and stress |
| RNAPII (POLR2A) | RNA polymerase II; its regulation is integral to DNA damage response | UV stalls RNAPII; coupling with translation ensures proteostasis |
| ATF4 | Stress-induced transcription factor; selectively translated upon eIF2α phosphorylation | Drives adaptive gene expression; survival vs apoptosis decisions |
| DDIT3 (CHOP) | Pro-apoptotic transcription factor induced by severe stress | Balances survival and death; marker of unresolved UV damage |
| RPS6KB1 (p70S6K) | mTOR downstream kinase; regulates translation initiation | Modulates recovery of translation after UV |
| EIF4EBP1 (4E-BP1) | Inhibits cap-dependent translation when hypophosphorylated | mTOR target; contributes to translational control |
| RPTOR (Raptor) | Component of mTORC1; regulates translation via 4E-BP1 and S6K | Integrates nutrient and stress signals |
| MAPKAPK2 (MK2) | Kinase involved in mRNA stability and translation | UV-activated; modulates inflammatory response |
| HNRNPA1 | RNA-binding protein; affects mRNA translation and splicing | UV-induced relocalization; stress granule component |
| TIA1 | Stress granule marker; regulates translation of specific mRNAs | UV induces stress granules; affects cell survival |
| EIF4E | Cap-binding protein; rate-limiting for translation initiation | Overexpressed in cancers; target for therapy |
| EIF4G1 | Scaffold for translation initiation complex | Cleaved during stress; modulates translation |
| PABPC1 | Poly(A)-binding protein; enhances translation | UV-induced modification affects translation |
| RACK1 | Ribosome-associated protein; regulates translation and stress responses | Involved in UV response; potential biomarker |
How Is regulation of translation involved in cellular response to UV Regulated?
The regulation of translation during the UV response is controlled by multiple signaling pathways. The integrated stress response, mediated by eIF2α kinases such as GCN2, is a primary mechanism. mTOR signaling also plays a role: UV can inhibit mTORC1, leading to dephosphorylation of 4E-BP1 and S6K, which further suppresses cap-dependent translation. Additionally, RNA-binding proteins like CIRBP and stress granule components modulate the translation of specific mRNAs. Autophagy and other stress pathways may cross-talk with translational control to determine cell fate.
regulation of translation involved in cellular response to UV and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| EIF4E | Cancer (melanoma, squamous cell carcinoma) | Overexpression in keratinocytes; xenograft models |
| GCN2 (EIF2AK4) | UV sensitivity, cancer | Knockout mice; cell lines with point mutations |
| CIRBP | Stress response, cancer | Knockout and overexpression models |
| E2F1 | Cancer, DNA damage response | Conditional knockout; point mutation |
| POLR2A | UV-sensitive syndrome, cancer | Knock-in of degradation-resistant mutants |
Cancer and UV-induced skin malignancies
Dysregulation of translation during the UV response can promote cancer. For example, overexpression of eIF4E enhances translation of pro-survival factors, contributing to melanoma and non-melanoma skin cancers. UV-induced translational reprogramming may also allow cancer cells to survive genotoxic stress and resist therapy. Targeting translation initiation factors is an emerging therapeutic strategy.
Neurodegeneration and chronic stress
In neurodegenerative diseases, chronic activation of the integrated stress response and dysregulated translation contribute to neuronal loss. UV is not a direct cause, but similar stress pathways are activated by protein aggregates and oxidative stress. Understanding UV-responsive translation may inform general mechanisms of stress-related neurodegeneration.
Ribosomopathies and translational defects
Mutations in ribosomal proteins or translation factors can lead to ribosomopathies, which often present with UV sensitivity and cancer predisposition. Studying GO:1904803 helps elucidate how defects in translational control manifest in these rare diseases.
From regulation of translation involved in cellular response to UV-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does GCN2 mediate UV-induced translational repression? | GCN2 knockout cell lines and mice |
| What is the role of CIRBP in UV survival? | CIRBP knockout and overexpression cells |
| How does eIF2α phosphorylation affect UV sensitivity? | Point mutation (S51A) knock-in cells |
| Which mRNAs are selectively translated after UV? | Ribo-seq in wild-type vs. mutant cells |
| Does E2F1 regulate translation-related genes? | E2F1 knockout and tagged knock-in |
| Can mTOR inhibition mimic UV-induced translation shutdown? | mTOR inhibitor treatment in cell lines |
How to Study the regulation of translation involved in cellular response to UV Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Ribo-seq | Genome-wide translation efficiency | Identify selectively translated mRNAs after UV |
| Polysome profiling | Distribution of mRNAs across polysomes | Validate global translation shutdown |
| Phospho-immunoblotting | Phosphorylation status of eIF2α, 4E-BP1 | Monitor stress kinase activation |
| CRISPR knockout | Loss-of-function phenotypes | Test necessity of candidate genes |
| CRISPR point mutation | Specific amino acid changes | Dissect phosphorylation sites |
| CRISPR knock-in | Tagged or mutant proteins | Track localization and interactions |
| RNA-seq | Transcriptome changes | Distinguish transcriptional vs. translational effects |
| Proteomics | Protein abundance and modifications | Global proteome remodeling after UV |
Ribosome profiling (Ribo-seq)
Ribo-seq provides a genome-wide snapshot of translating ribosomes at codon resolution. It is ideal for identifying mRNAs that escape global translational repression after UV and for quantifying changes in translation efficiency.
Polysome profiling
Polysome profiling separates mRNAs by the number of ribosomes bound, allowing assessment of global translation and specific mRNA recruitment to polysomes. It is useful for validating Ribo-seq findings and studying dynamic changes.
Phospho-specific immunoblotting
Western blotting with antibodies against phosphorylated eIF2α, 4E-BP1, and S6K is a standard method to monitor key signaling events in UV-induced translational control.
CRISPR-based gene editing
Knockout, point mutation, and knock-in models enable causal testing of candidate genes. For example, introducing the S51A mutation in eIF2α prevents phosphorylation and blocks translational repression.
How CRISPR Can Be Used to Study GO:1904803 regulation of translation involved in cellular response to UV
Knockout
CRISPR knockout of genes like GCN2 or CIRBP allows researchers to test their requirement for UV-induced translational control. For example, GCN2 knockout cells fail to phosphorylate eIF2α and show altered survival after UV.
Point Mutation
Introducing precise point mutations, such as the S51A mutation in eIF2α, can block phosphorylation and prevent translational repression. This helps dissect the specific contribution of phosphorylation events.
Knock-in
Knock-in of tagged versions of proteins (e.g., GFP-CIRBP) enables live-cell imaging and interaction studies. It also allows expression of mutant proteins under endogenous regulation.
Overexpression
Overexpression of translation factors like eIF4E or RNA-binding proteins can mimic pathological states and test sufficiency in driving UV resistance or transformation.
How EDITGENE Supports regulation of translation involved in cellular response to UV Research
Researchers studying regulation of translation involved in cellular response to UV-related genes often need to determine whether a candidate gene is causally involved in translational control, DNA repair, or cell survival. EDITGENE provides comprehensive CRISPR services to generate precisely engineered cell models, enabling rigorous mechanistic studies.
Contact EDITGENE today to design your custom CRISPR model for regulation of translation involved in cellular response to UV research.
Frequently Asked Questions About regulation of translation involved in cellular response to UV
What is GO:1904803?
GO:1904803 is a Gene Ontology term for any regulation of translation that occurs as part of the cellular response to UV radiation.
What genes are involved in regulation of translation involved in cellular response to UV?
Key genes include EIF2S1 (eIF2α), GCN2, PERK, CIRBP, E2F1, and RNAPII subunits.
How does UV affect protein synthesis?
UV activates stress kinases that phosphorylate eIF2α, leading to global translational repression while allowing selective translation of repair and survival factors.
What is the role of eIF2α in UV response?
Phosphorylation of eIF2α inhibits translation initiation, conserving resources and promoting adaptive gene expression.
Which methods are used to study translation after UV?
Ribo-seq, polysome profiling, phospho-immunoblotting, and CRISPR-based editing are commonly used.
Is regulation of translation involved in cellular response to UV linked to cancer?
Yes, dysregulation can promote skin cancer by enhancing survival and proliferation of damaged cells.
What is CIRBP and how does it relate to UV?
CIRBP is a cold-inducible RNA-binding protein that is also induced by UV and modulates translation of specific mRNAs to promote survival.
Can CRISPR be used to study UV-responsive translation?
Yes, CRISPR knockout, point mutation, and knock-in models are powerful tools to dissect gene function in this process.
What are stress granules and their role in UV response?
Stress granules are cytoplasmic aggregates of RNA and proteins that form upon UV and regulate translation and cell survival.
How does mTOR signaling interact with UV-induced translation control?
UV can inhibit mTORC1, leading to dephosphorylation of 4E-BP1 and S6K, which contributes to translational repression.
Conclusion
GO:1904803 encompasses the critical regulatory events that control protein synthesis during the cellular response to UV. This process is essential for cell survival, DNA repair, and tissue homeostasis, and its dysregulation is linked to cancer and other diseases. By leveraging advanced CRISPR models and multi-omics methods, researchers can uncover the precise mechanisms and identify therapeutic targets. EDITGENE offers comprehensive services to support these investigations.
References
- 1. Foerster EG et al.. 2022. How autophagy controls the intestinal epithelial barrier.. Autophagy 18(1):86-103 PMID: 33906557
- 2. Corre M et al.. 2024. Regulation of cold-inducible RNA-binding protein (CIRBP) in response to cellular stresses.. Biochimie 217:3-9 PMID: 37037339
- 3. Pangilinan C et al.. 2024. Emerging dimensions of autophagy in melanoma.. Autophagy 20(8):1700-1711 PMID: 38497492
- 4. Anda S et al.. 2017. Activation of Gcn2 in response to different stresses.. PLoS One 12(8):e0182143 PMID: 28771613
- 6. Tufegdžić Vidaković A et al.. 2020. Regulation of the RNAPII Pool Is Integral to the DNA Damage Response.. Cell 180(6):1245-1261.e21 PMID: 32142654
- 7. Biswas AK et al.. 2012. Transcriptional and nontranscriptional functions of E2F1 in response to DNA damage.. Cancer Res 72(1):13-7 PMID: 22180494
- 8. Mullenders LHF . 2018. Solar UV damage to cellular DNA: from mechanisms to biological effects.. Photochem Photobiol Sci 17(12):1842-1852 PMID: 30065996
