negative regulation of cytoplasmic translation

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of cytoplasmic translation. [GOC:obol]

Negative regulation of cytoplasmic translation is a complex process that involves a variety of mechanisms to control the rate of protein synthesis in the cytoplasm. This regulation is crucial for maintaining cellular homeostasis, responding to environmental changes, and controlling cell growth and differentiation. Here’s a detailed breakdown of the key mechanisms involved:

1. **Regulation at the Initiation Stage:**
- **eIF2 Phosphorylation:** The eukaryotic initiation factor 2 (eIF2) is a key regulator of translation initiation. When eIF2 is phosphorylated, it binds to the guanine nucleotide exchange factor eIF2B, inhibiting its activity. This results in reduced formation of the ternary complex (eIF2-GTP-methionine tRNA), which is essential for initiating translation. Phosphorylation of eIF2 can be triggered by various stress signals, including nutrient deprivation, viral infection, and unfolded protein stress.
- **mTOR Signaling Pathway:** The mechanistic target of rapamycin (mTOR) is a central regulator of cell growth and metabolism. mTOR activation promotes protein synthesis by stimulating the phosphorylation of eIF2B, leading to increased formation of the ternary complex and enhanced translation initiation.

2. **Regulation at the Elongation Stage:**
- **Ribosome Stalling:** Ribosomes can stall during translation elongation due to various factors, such as the presence of rare codons or secondary structures in mRNA. This stalling can trigger quality control mechanisms that lead to ribosome recycling or mRNA degradation.
- **Regulation by MicroRNAs (miRNAs):** miRNAs are small non-coding RNAs that can bind to target mRNAs and inhibit their translation. By targeting specific mRNAs, miRNAs can fine-tune protein expression and contribute to the negative regulation of translation.

3. **Regulation at the Termination Stage:**
- **Release Factors (RFs):** Release factors (RF1 and RF2) recognize stop codons in mRNA and trigger the release of the polypeptide chain from the ribosome. This process is essential for terminating translation.

4. **Other Mechanisms:**
- **mRNA Degradation:** The stability of mRNAs can be regulated, and degradation of mRNAs can lead to a decrease in protein synthesis.
- **Translational Repression by RNA-binding Proteins:** Specific RNA-binding proteins can bind to mRNAs and repress their translation. These proteins often recognize specific sequences or structures in mRNAs and can act as translation repressors.

In summary, negative regulation of cytoplasmic translation is a multi-layered process involving control at various steps of translation initiation, elongation, and termination. These regulatory mechanisms are essential for maintaining cellular homeostasis, responding to environmental changes, and controlling cell growth and differentiation.'
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Proteins (3)

Compounds (29)