Translation - mRNA to Protein

Overview of Translation

Translation occurs in the cytoplasm on ribosomes - molecular machines composed of rRNA and proteins. Ribosomes can be free-floating in the cytoplasm or attached to the rough endoplasmic reticulum (ER).

The ribosome has three binding sites for tRNA molecules: the A site (aminoacyl - where incoming tRNA arrives), the P site (peptidyl - where the growing chain is held), and the E site (exit - where empty tRNA leaves).

The Genetic Code

The mRNA message is read in groups of three nucleotides called codons. Each codon specifies one of the 20 amino acids or a stop signal:

• Start codon: AUG - codes for methionine and signals the beginning of translation
• Stop codons: UAA, UAG, UGA - signal the end of translation (no amino acid is added)
• 64 total codons code for 20 amino acids + 3 stop signals
• The code is degenerate - most amino acids are encoded by more than one codon
• The code is universal - nearly all organisms use the same codon assignments

The Three Stages of Translation

1. Initiation

The small ribosomal subunit binds to the mRNA near the 5' cap and scans along until it finds the start codon AUG. An initiator tRNA carrying methionine binds to the AUG in the P site. The large ribosomal subunit then joins, forming the complete ribosome. This process requires initiation factors and GTP energy.

2. Elongation

Elongation is a repeating three-step cycle:

1. Codon recognition - a tRNA with the correct anticodon enters the A site
2. Peptide bond formation - the ribosome catalyzes a peptide bond between the amino acid in the A site and the growing chain in the P site (this is done by the rRNA itself, acting as a ribozyme)
3. Translocation - the ribosome shifts one codon along the mRNA, moving the tRNA from A to P and from P to E (where it exits)

This cycle repeats at a rate of roughly 15-20 amino acids per second in eukaryotes. Multiple ribosomes can translate the same mRNA simultaneously, forming a structure called a polyribosome (polysome).

3. Termination

When the ribosome reaches a stop codon (UAA, UAG, or UGA), no tRNA can bind. Instead, a release factor protein enters the A site. This triggers the ribosome to release the completed polypeptide chain and dissociate into its two subunits.

Ribosome Structure

tRNA - The Adapter Molecule

Transfer RNA (tRNA) acts as the bridge between the nucleic acid language of mRNA and the amino acid language of proteins:

• Each tRNA is 76-90 nucleotides long and folds into a characteristic cloverleaf shape
• The anticodon (3 bases) on tRNA is complementary to a codon on mRNA
• The 3' end (CCA tail) carries the specific amino acid
• Aminoacyl-tRNA synthetase enzymes charge each tRNA with its correct amino acid - there is one enzyme for each of the 20 amino acids
• Wobble pairing allows the third position of the codon to pair less strictly, which is why multiple codons can code for the same amino acid

From Polypeptide to Functional Protein

The polypeptide chain released from the ribosome is not yet a functional protein. It must fold into a specific three-dimensional shape, and may undergo additional modifications. These post-translational modifications are covered in the next chapter.