Page last updated: 2024-10-24

endoribonuclease activity, cleaving siRNA-paired mRNA

Definition

Target type: molecularfunction

Catalysis of the endonucleolytic cleavage of the mRNA in a double-stranded RNA molecule formed by the base pairing of an mRNA with an siRNA, yielding 5'-phosphomonoesters. [GOC:mah, PMID:15105377]

Endoribonuclease activity, cleaving siRNA-paired mRNA, refers to the enzymatic process of cleaving a messenger RNA (mRNA) molecule that is specifically bound by a small interfering RNA (siRNA) duplex. This process is essential for RNA interference (RNAi), a cellular mechanism that regulates gene expression by silencing the translation of specific mRNAs.

Here's a detailed description of the molecular function:

1. **siRNA Binding:** The process begins with the recognition and binding of an siRNA duplex to its target mRNA. The siRNA duplex consists of two complementary strands: a guide strand and a passenger strand. The guide strand, with its complementary sequence to the target mRNA, directs the siRNA to its target.

2. **Target mRNA Recognition:** The guide strand of the siRNA base pairs with the target mRNA, forming a double-stranded RNA (dsRNA) structure. This pairing is highly specific, ensuring that only the intended mRNA is targeted.

3. **Endoribonuclease Activity:** The endoribonuclease enzyme, often known as a "Dicer" in the context of RNAi, recognizes the dsRNA structure formed between the siRNA and the target mRNA. The enzyme then cleaves the target mRNA within the dsRNA region, typically 2 nucleotides away from the 5' end of the guide strand.

4. **mRNA Degradation:** The cleavage of the target mRNA by the endoribonuclease disrupts its structure and renders it unable to be translated into a protein. The cleaved fragments are then degraded by other cellular enzymes, effectively silencing the expression of the targeted gene.

5. **Specificity and Regulation:** The specificity of this process is ensured by the precise base pairing between the siRNA guide strand and the target mRNA. The activity of the endoribonuclease is regulated by factors like the concentration of siRNA and the availability of other cellular components involved in RNAi.

This mechanism of siRNA-mediated mRNA cleavage plays a crucial role in gene regulation, defense against viral infections, and therapeutic interventions in various diseases.'
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Proteins (1)

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

Compounds (4)

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