formation of translation preinitiation complex

Definition

Target type: biologicalprocess

The joining of the small ribosomal subunit, ternary complex, and mRNA. [GOC:hjd]

The translation preinitiation complex (PIC) is a crucial assembly of factors that initiates protein synthesis. Its formation is a complex and highly regulated process, involving multiple steps:

1. **Recruitment of the 40S ribosomal subunit:** The small ribosomal subunit (40S) binds to the 5' cap of the mRNA, facilitated by the cap-binding complex (CBC). This interaction is essential for the correct positioning of the ribosome on the mRNA.

2. **Binding of eIF1, eIF1A, and eIF3:** These initiation factors associate with the 40S subunit, contributing to its stability and setting the stage for further assembly.

3. **Loading of the initiator methionine tRNA (Met-tRNAi):** This special tRNA carries the methionine amino acid, which will be the first amino acid incorporated into the polypeptide chain. eIF2, a GTP-binding protein, plays a vital role in recruiting Met-tRNAi to the 40S subunit.

4. **Scanning for the start codon:** The 40S subunit, together with its associated factors, moves along the mRNA in a 5' to 3' direction, searching for the AUG start codon. This process, known as scanning, is driven by the hydrolysis of ATP. eIF1 and eIF1A are involved in promoting the linear movement of the ribosome along the mRNA.

5. **Recognition of the start codon:** Upon encountering the AUG start codon, the 40S subunit pauses. eIF1 and eIF1A dissociate, and eIF5, another initiation factor, is recruited. This interaction stimulates the hydrolysis of GTP bound to eIF2, triggering conformational changes in the complex.

6. **Joining of the 60S ribosomal subunit:** The large ribosomal subunit (60S) joins the 40S subunit, forming the complete 80S ribosome. This step is mediated by eIF5B, a GTPase that also hydrolyzes GTP to drive the association of the 60S subunit.

7. **Release of initiation factors:** Following the formation of the 80S ribosome, most initiation factors are released, leaving the ribosome ready to initiate translation. eIF2, however, remains associated with the 80S ribosome and is ready to participate in another round of initiation.

The final preinitiation complex comprises the 80S ribosome, the initiator Met-tRNAi bound to the P-site, and eIF2 bound to the 80S ribosome. This complex is poised to initiate translation and synthesize the protein encoded by the mRNA.

It is important to note that the assembly and disassembly of the PIC are highly regulated processes. Factors such as phosphorylation of initiation factors, availability of GTP, and the presence of specific mRNA sequences can influence the efficiency and fidelity of initiation. These regulatory mechanisms ensure that translation is initiated only at the appropriate time and in the correct context.'
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Proteins (1)

Compounds (1)