Page last updated: 2024-10-24

mRNA 3'-UTR AU-rich region binding

Definition

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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Proteins (3)

ProteinDefinitionTaxonomy
Protein argonaute-2A protein argonaute-2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9UKV8]Homo sapiens (human)
ELAV-like protein 1An ELAV-like protein 1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15717]Homo sapiens (human)
ELAV-like protein 3An ELAV-like protein 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14576]Homo sapiens (human)

Compounds (11)

CompoundDefinitionClassesRoles
sulfaguanidinesulfaguanidine : 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 antibioticantiinfective agent
sulfanilamidesubstituted aniline;
sulfonamide;
sulfonamide antibiotic
antibacterial agent;
drug allergen;
EC 4.2.1.1 (carbonic anhydrase) inhibitor
sulfisomidinesulfisomidine : 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 monophosphateuridine 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)furanone5,8-dihydroxy-3-methyl-4-(9H)-naphtho(2,3-c)furanone: isolated from Micromonospora sp. KY7123; structure given in first source
quercetin7-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
myricetin7-hydroxyflavonol;
hexahydroxyflavone
antineoplastic agent;
antioxidant;
cyclooxygenase 1 inhibitor;
food component;
geroprotector;
hypoglycemic agent;
plant metabolite
rhamnetinrhamnetin : A monomethoxyflavone that is quercetin methylated at position 7.

rhamnetin: aglycone of xanthorhamnin; from Rhamnus
monomethoxyflavone;
tetrahydroxyflavone
anti-inflammatory agent;
antioxidant;
metabolite
ellagic acidcatechols;
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 Idihydrotanshinone I: extracted from Radix Salviaeabietane diterpenoidanticoronaviral agent