Initiation of Translation: How Protein Synthesis Begins
- Imagine you’re assembling a complex machine.
- Before you start, you need the right tools, instructions, and a clear starting point.
- In cells, this process begins with translation initiation, the first step in building proteins from mRNA.
The Key Players in Translation
- Before diving into initiation, let’s review the essential components:
- mRNA: Carries the genetic instructions from DNA.
- Ribosome: The molecular machine that reads mRNA and assembles amino acids.
- tRNA: Transfers the correct amino acids to the ribosome.
Step-by-Step Process of Translation Initiation
1. Attachment of the Small Ribosomal Subunit
- The process begins with the small subunit of the ribosome binding to the 5′ end of the mRNA.
- This end is marked by a 5′ cap in eukaryotes, which helps the ribosome recognize and attach to the mRNA.
In prokaryotes, the small subunit binds to a specific sequence called the Shine-Dalgarno sequence.
2. Scanning for the Start Codon
- Once attached, the small subunit moves along the mRNA in the 5′ to 3′ direction, scanning for the start codon (AUG).
- This codon signals where translation should begin.
3. Binding of the Initiator tRNA
- The start codon AUG codes for the amino acid methionine.
- A special tRNA, called the initiator tRNA, carries methionine and has an anticodon (UAC) that pairs with AUG.
- This tRNA binds to the P site of the small ribosomal subunit.
The initiator tRNA is unique because it is the only tRNA that can bind directly to the P site during initiation.
4. Attachment of the Large Ribosomal Subunit
- Once the initiator tRNA is in place, the large ribosomal subunit joins the small subunit.
- This forms a complete ribosome, ready to begin translation.
- The initiator tRNA remains in the P site, while the A site is empty and ready to accept the next tRNA.
- In eukaryotes, the start codon is usually the first AUG encountered by the ribosome.
- In prokaryotes, the start codon is often located near the Shine-Dalgarno sequence.
The Role of Ribosomal Binding Sites: A, P, and E
- The ribosome has three critical binding sites for tRNA:
- A Site (Aminoacyl Site): Holds the tRNA carrying the next amino acid to be added.
- P Site (Peptidyl Site): Holds the tRNA with the growing polypeptide chain.
- E Site (Exit Site): Where tRNA, now empty, exits the ribosome.
Don’t confuse the order of the binding sites. The sequence is A (arrival), P (polypeptide), E (exit).
Initiation Sets the Stage for Accurate Protein Synthesis
- Without it, the ribosome might start translating at the wrong codon, leading to a completely different and nonfunctional protein.
- How does the universality of the start codon (AUG) reflect the shared evolutionary history of life?
- Could this universality have implications for synthetic biology?


