negative regulation of selenocysteine incorporation

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of selenocysteine incorporation. [GO_REF:0000058, GOC:TermGenie, PMID:21685449]

Negative regulation of selenocysteine incorporation is a complex process that involves the interplay of various molecular components, including specific RNA sequences, proteins, and cofactors. The incorporation of selenocysteine, the 21st amino acid, into proteins is essential for the function of numerous selenoproteins involved in diverse biological processes, such as antioxidant defense, thyroid hormone metabolism, and immune regulation. However, dysregulation of selenocysteine incorporation can lead to various pathologies. Here's a detailed description of the negative regulation of selenocysteine incorporation:

1. **Secis Element Recognition:** Selenocysteine incorporation relies on a specific RNA sequence known as the SECIS element (selenocysteine insertion sequence). This element is located within the 3' untranslated region (UTR) of selenoprotein mRNAs. Negative regulation can occur at the level of SECIS element recognition. Specific factors, such as SECIS binding protein 2 (SBP2), can bind to the SECIS element and prevent its recognition by the selenocysteine insertion machinery.

2. **Selenocysteine Synthase Inhibition:** Selenocysteine synthase (SecS) is the enzyme responsible for synthesizing selenocysteine from serine and selenophosphate. Negative regulation can occur at the level of SecS activity. Specific inhibitors, such as selenophosphate synthetase (SPS) inhibitors, can disrupt SecS function, preventing the formation of selenocysteine.

3. **EFSec Inhibition:** Elongation factor for selenocysteine (EFSec) is a translation factor that delivers selenocysteine to the ribosome during protein synthesis. Negative regulation can occur at the level of EFSec activity. Specific inhibitors, such as those targeting the GTPase activity of EFSec, can prevent its function.

4. **Ribosomal Stalling:** The ribosome can stall during selenocysteine incorporation due to various factors, such as insufficient SECIS element recognition or EFSec availability. This stalling can activate quality control mechanisms, leading to the degradation of the nascent selenoprotein, thereby negatively regulating selenocysteine incorporation.

5. **MicroRNA Regulation:** MicroRNAs (miRNAs) are small non-coding RNAs that can regulate gene expression at the post-transcriptional level. Specific miRNAs can target the 3' UTR of selenoprotein mRNAs and inhibit their translation, thereby negatively regulating selenocysteine incorporation.

In summary, negative regulation of selenocysteine incorporation can occur at multiple levels, including recognition of the SECIS element, selenocysteine synthesis, EFSec activity, ribosomal stalling, and microRNA regulation. These mechanisms ensure the precise control of selenocysteine incorporation and the proper balance of selenoprotein synthesis. Dysregulation of these mechanisms can lead to pathological consequences.
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