Target type: molecularfunction
Binding to a region containing frequent adenine and uridine bases within the 3' untranslated region of a mRNA molecule or in pre-mRNA intron. The ARE-binding element consensus is UUAUUUAUU. ARE-binding proteins control the stability and/or translation of mRNAs. [GOC:vw, PMID:31511872, PMID:7892223, PMID:8578590]
The 3'-untranslated region (3'-UTR) of messenger RNA (mRNA) often contains AU-rich elements (AREs) that play a crucial role in regulating mRNA stability and translation. These AREs are recognized by specific RNA-binding proteins (RBPs), which can either enhance or repress mRNA decay and translation.
The molecular function of ARE-binding proteins is multifaceted and highly context-dependent:
**1. mRNA Destabilization:**
- Certain RBPs, such as tristetraprolin (TTP) and AUF1, bind to AREs and promote mRNA degradation through recruitment of the deadenylase complex and exonucleases.
- Deadenylation, the removal of the poly(A) tail, initiates the degradation process, followed by 5' to 3' exonucleolytic decay.
**2. mRNA Stabilization:**
- Some RBPs, including HuR and ELAVL1, bind to AREs and protect mRNA from degradation.
- These proteins can stabilize the poly(A) tail, prevent deadenylation, and potentially shield the mRNA from the degradation machinery.
**3. Translation Regulation:**
- ARE-binding proteins can influence translation initiation or elongation.
- Some RBPs enhance translation, while others can suppress it.
- The specific effect on translation depends on the specific RBP, its binding site, and the cellular context.
**4. MicroRNA (miRNA) Targeting:**
- AREs can also serve as binding sites for miRNAs.
- miRNAs can regulate mRNA stability and translation through interactions with AREs.
**5. Stress Response:**
- The 3'-UTR and AREs are critical for mediating mRNA responses to cellular stress conditions such as inflammation, hypoxia, and oxidative stress.
- Stress-induced changes in ARE-binding protein expression or activity can influence the stability and translation of specific mRNAs, contributing to the cellular response.
In summary, the molecular function of mRNA 3'-UTR AU-rich region binding is a complex and dynamic process that involves the interaction of various RBPs with AREs. This interaction plays a critical role in regulating mRNA stability, translation, and overall gene expression, and it is intimately linked to cellular responses to diverse stimuli and stress conditions.'
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Protein | Definition | Taxonomy |
---|---|---|
Protein argonaute-2 | A protein argonaute-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UKV8] | Homo sapiens (human) |
ELAV-like protein 1 | An ELAV-like protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15717] | Homo sapiens (human) |
ELAV-like protein 3 | An ELAV-like protein 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14576] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
sulfaguanidine | sulfaguanidine : A sulfonamide incorporating a guanidine moiety used to block the synthesis of folic acid; mostly used in veterinary medicine Sulfaguanidine: A sulfanilamide antimicrobial agent that is used to treat enteric infections. | sulfonamide antibiotic | antiinfective agent |
sulfanilamide | substituted aniline; sulfonamide; sulfonamide antibiotic | antibacterial agent; drug allergen; EC 4.2.1.1 (carbonic anhydrase) inhibitor | |
sulfisomidine | sulfisomidine : A sulfonamide consisting of pyrimidine having methyl substituents at the 2- and 6-positions and a 4-aminobenzenesulfonamido group at the 4-position. Sulfisomidine: A sulfanilamide antibacterial agent. | pyrimidines; sulfonamide; sulfonamide antibiotic | antiinfective agent |
uridine monophosphate | uridine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having uracil as the nucleobase. Uridine Monophosphate: 5'-Uridylic acid. A uracil nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position. | pyrimidine ribonucleoside 5'-monophosphate; uridine 5'-phosphate | Escherichia coli metabolite; human metabolite; mouse metabolite |
epicatechin gallate | (-)-epicatechin-3-O-gallate : A gallate ester obtained by formal condensation of the carboxy group of gallic acid with the (3R)-hydroxy group of epicatechin. A natural product found in Parapiptadenia rigida. epicatechin gallate: a steroid 5alpha-reductase inhibitor; RN given refers to the (cis)-isomer; structure given in first source; isolated from green tea | catechin; gallate ester; polyphenol | EC 3.2.1.1 (alpha-amylase) inhibitor; EC 3.2.1.20 (alpha-glucosidase) inhibitor; metabolite |
5,8-dihydroxy-3-methyl-4-(9h)-naphtho(2,3-c)furanone | 5,8-dihydroxy-3-methyl-4-(9H)-naphtho(2,3-c)furanone: isolated from Micromonospora sp. KY7123; structure given in first source | ||
quercetin | 7-hydroxyflavonol; pentahydroxyflavone | antibacterial agent; antineoplastic agent; antioxidant; Aurora kinase inhibitor; chelator; EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor; geroprotector; phytoestrogen; plant metabolite; protein kinase inhibitor; radical scavenger | |
myricetin | 7-hydroxyflavonol; hexahydroxyflavone | antineoplastic agent; antioxidant; cyclooxygenase 1 inhibitor; food component; geroprotector; hypoglycemic agent; plant metabolite | |
rhamnetin | rhamnetin : A monomethoxyflavone that is quercetin methylated at position 7. rhamnetin: aglycone of xanthorhamnin; from Rhamnus | monomethoxyflavone; tetrahydroxyflavone | anti-inflammatory agent; antioxidant; metabolite |
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 | |
Dihydrotanshinone I | dihydrotanshinone I: extracted from Radix Salviae | abietane diterpenoid | anticoronaviral agent |