positive regulation of cap-dependent translational initiation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of cap-dependent translational initiation. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie, PMID:11959995]

Positive regulation of cap-dependent translational initiation is a crucial process in eukaryotic cells that controls the rate of protein synthesis. It is initiated by the binding of the eukaryotic initiation factor 4F (eIF4F) complex to the 5' cap of mRNA. eIF4F is a trimeric complex composed of eIF4E, eIF4A, and eIF4G. eIF4E, the cap-binding protein, recognizes and binds to the 5' cap structure, which is a 7-methylguanosine residue. eIF4A, a helicase, unwinds any secondary structure in the 5' untranslated region (UTR) of the mRNA, allowing the ribosome to access the initiation codon. eIF4G serves as a scaffolding protein that links eIF4E and eIF4A to the 40S ribosomal subunit, as well as to other initiation factors, such as eIF3 and eIF5. This intricate interplay of initiation factors facilitates the recruitment of the 40S ribosomal subunit to the mRNA, and subsequently, the formation of the 80S initiation complex. The 80S initiation complex then scans along the mRNA in search of the AUG start codon, which signals the beginning of protein synthesis. The initiation of translation can be positively regulated by various mechanisms, including:
- **Phosphorylation of eIF4E:** This phosphorylation event enhances the binding affinity of eIF4E to the 5' cap, promoting mRNA recruitment and initiation complex formation.
- **Increased eIF4E expression:** Higher levels of eIF4E can lead to enhanced cap-dependent translation by providing more binding sites for the 5' cap.
- **Activation of eIF4G:** The activity of eIF4G can be regulated by factors such as mTOR signaling pathway, which promotes its phosphorylation and activation.
- **Regulation of mRNA accessibility:** Factors that influence mRNA secondary structure and accessibility to the initiation complex can also affect cap-dependent translation. This includes mRNA modifications, binding of regulatory proteins, and cellular stress responses.
Positive regulation of cap-dependent translational initiation is essential for maintaining cellular homeostasis, responding to environmental cues, and orchestrating various cellular processes. Dysregulation of this process can lead to developmental defects, disease states, and even cancer.
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Proteins (1)

Compounds (1)