Page last updated: 2024-10-24

global gene silencing by mRNA cleavage

Definition

Target type: biologicalprocess

A posttranscriptional gene silencing pathway that involves the cleavage of mRNAs in a non-gene-specific manner. [PMID:15009896]

Global gene silencing by mRNA cleavage is a fundamental regulatory mechanism in eukaryotic cells. It involves the degradation of messenger RNA (mRNA) molecules, preventing the translation of specific genes into proteins. This process is crucial for maintaining cellular homeostasis, controlling development, and responding to environmental cues.

The process typically involves the following steps:

1. **Initiation:** The silencing pathway is triggered by specific signals, such as viral infection or stress. These signals activate specific proteins, known as RNA-induced silencing complexes (RISCs).
2. **Target recognition:** RISCs contain small interfering RNA (siRNA) molecules, which are short double-stranded RNA sequences that are complementary to specific mRNA targets. The siRNA guides the RISC to the target mRNA.
3. **mRNA cleavage:** Once the RISC encounters its target mRNA, the siRNA strand within the RISC acts as a guide, aligning the RISC with the complementary mRNA sequence. The RISC then utilizes an endonuclease activity to cleave the target mRNA at a specific site within the siRNA-binding region.
4. **mRNA degradation:** The cleaved mRNA fragments are unstable and are rapidly degraded by cellular exonucleases, effectively silencing the gene.

Several key protein players are involved in this process:

* **Dicer:** This enzyme processes double-stranded RNA into siRNAs.
* **Argonaute (AGO):** This protein is the catalytic component of the RISC and is responsible for mRNA cleavage.
* **RNA-dependent RNA polymerase (RdRP):** This enzyme amplifies the silencing signal by generating more siRNAs from existing target mRNA.

Global gene silencing by mRNA cleavage has diverse biological functions:

* **Defense against viruses:** This process is a primary defense mechanism against viral infections, as viruses rely on host cells for replication.
* **Regulation of gene expression:** mRNA cleavage can fine-tune gene expression levels in response to various stimuli, ensuring proper cellular function.
* **Development and differentiation:** This process plays a vital role in development, controlling the expression of genes required for cell fate determination and tissue formation.
* **Stress response:** mRNA cleavage can mediate cellular responses to stress, such as heat shock or nutrient deprivation.

Understanding the intricate details of global gene silencing by mRNA cleavage is essential for unraveling the complexity of gene regulation and cellular function. This knowledge has significant implications for the development of therapeutic interventions, including gene editing and antiviral therapies.'
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Proteins (1)

ProteinDefinitionTaxonomy
RISC-loading complex subunit TARBP2A RISC-loading complex subunit TARBP2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15633]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
enoxacinenoxacin : A 1,8-naphthyridine derivative that is 1,4-dihydro-1,8-naphthyridine with an ethyl group at the 1 position, a carboxy group at the 3-position, an oxo sustituent at the 4-position, a fluoro substituent at the 5-position and a piperazin-1-yl group at the 7 position. An antibacterial, it is used in the treatment of urinary-tract infections and gonorrhoea.

Enoxacin: A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID.
1,8-naphthyridine derivative;
amino acid;
fluoroquinolone antibiotic;
monocarboxylic acid;
N-arylpiperazine;
quinolone antibiotic
antibacterial drug;
DNA synthesis inhibitor
schisanhenol bschisanhenol B: isolated from kernels of Schisandra rubriflora; structure given in first source
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