Target type: biologicalprocess
Any regulation of mRNA stability that is involved in cellular response to UV. [GO_REF:0000060, GOC:TermGenie, PMID:10954610]
UV irradiation triggers a complex cellular response aimed at mitigating DNA damage and restoring cellular homeostasis. A key aspect of this response involves the regulation of mRNA stability, a process that controls the lifespan and abundance of messenger RNA molecules. The intricate interplay of various regulatory mechanisms ensures that transcripts essential for DNA repair and cell survival are preserved, while transcripts promoting cell cycle progression or those potentially damaged by UV are degraded.
1. **RNA-Binding Proteins (RBPs):** These proteins play a central role in mRNA stability regulation. Specific RBPs bind to specific sequences within mRNA, influencing its stability. In response to UV, certain RBPs like HuR and AUF1 relocate to the cytoplasm, where they bind to target mRNAs and promote their stabilization. These stabilized transcripts often encode proteins involved in DNA repair, cell cycle arrest, and UV-induced apoptosis. Conversely, other RBPs like TTP and tristetraprolin (TTP) are upregulated upon UV exposure and promote the degradation of mRNAs encoding pro-inflammatory cytokines or cell cycle regulators, preventing excessive inflammation or uncontrolled cell division.
2. **MicroRNAs (miRNAs):** These small non-coding RNA molecules regulate gene expression by binding to target mRNAs, leading to their degradation or translational repression. Specific miRNAs are differentially regulated in response to UV exposure, contributing to the fine-tuning of mRNA stability. For instance, miR-21, known to promote cell proliferation, is upregulated after UV exposure, potentially contributing to the observed increase in cell survival. Conversely, miRNAs like miR-125b and miR-34a, which are involved in cell cycle arrest and apoptosis, are downregulated in response to UV.
3. **Decapping Enzymes:** The 5' cap structure protects mRNA from degradation. Decapping enzymes remove this cap, rendering the mRNA susceptible to degradation. UV-induced DNA damage can trigger the upregulation of decapping enzymes, promoting the degradation of specific mRNAs, including those encoding proteins that could be detrimental to cell survival or those whose translation could further exacerbate DNA damage.
4. **Exonucleases:** These enzymes degrade mRNA from the 3' or 5' end. UV exposure can alter the activity of specific exonucleases, leading to selective degradation of mRNAs. For instance, the exonuclease XRN1, which degrades mRNA from the 5' end, is upregulated after UV exposure, contributing to the clearance of mRNAs potentially damaged by UV.
5. **Polyadenylation:** The poly(A) tail at the 3' end of mRNA contributes to its stability. UV exposure can lead to changes in polyadenylation, either shortening or lengthening the poly(A) tail, influencing mRNA stability. For example, specific mRNAs involved in DNA repair undergo poly(A) tail lengthening, increasing their stability and promoting their translation.
6. **Autophagy:** This cellular process involves the breakdown and recycling of cellular components, including mRNAs. UV exposure can trigger autophagy, selectively degrading mRNAs whose products could be detrimental in the context of DNA damage.
These intricate regulatory mechanisms ensure a precise and dynamic control of mRNA stability in response to UV, ultimately contributing to the cellular response to UV-induced damage and influencing the fate of the cell.'
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Protein | Definition | Taxonomy |
---|---|---|
Nucleophosmin | A nucleophosmin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06748] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
imatinib | aromatic amine; benzamides; N-methylpiperazine; pyridines; pyrimidines | antineoplastic agent; apoptosis inducer; tyrosine kinase inhibitor | |
pd 173955 | PD 173955: inhibits src family-selective tyrosine kinase; structure in first source | aryl sulfide; dichlorobenzene; methyl sulfide; pyridopyrimidine | tyrosine kinase inhibitor |
ellagic acid | catechols; cyclic ketone; lactone; organic heterotetracyclic compound; polyphenol | antioxidant; EC 1.14.18.1 (tyrosinase) inhibitor; EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor; EC 2.4.1.1 (glycogen phosphorylase) inhibitor; EC 2.5.1.18 (glutathione transferase) inhibitor; EC 2.7.1.127 (inositol-trisphosphate 3-kinase) inhibitor; EC 2.7.1.151 (inositol-polyphosphate multikinase) inhibitor; EC 2.7.4.6 (nucleoside-diphosphate kinase) inhibitor; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; food additive; fungal metabolite; geroprotector; plant metabolite; skin lightening agent | |
bosutinib | 4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile: a Src kinase inhibitor; structure in first source | aminoquinoline; aromatic ether; dichlorobenzene; N-methylpiperazine; nitrile; tertiary amino compound | antineoplastic agent; tyrosine kinase inhibitor |
crizotinib | crizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER. | 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine | antineoplastic agent; biomarker; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |
ceritinib | ceritinib : A member of the class of aminopyrimidines that is 2,6-diamino-5-chloropyrimidine in which the amino groups at positions 2 and 6 are respectively carrying 2-methoxy-4-(piperidin-4-yl)-5-methylphenyl and 2-(isopropylsulfonyl)phenyl substituents. Used for the treatment of ALK-positive metastatic non-small cell lung cancer. ceritinib: an anaplastic lymphoma kinase inhibitor | aminopyrimidine; aromatic ether; organochlorine compound; piperidines; secondary amino compound; sulfone | antineoplastic agent; EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor |