Translation

Translation begins when the small ribosomal subunit, complexed with methionine tRNA and initiation factors, binds to the five prime end of mRNA. The complex scans the mRNA in the five prime to three prime direction until it encounters an AUG codon, which serves as the translation initiation site. The methionine tRNA then pairs with this AUG codon and recruits the large ribosomal subunit, positioning the ribosome to begin protein synthesis.

Transfer RNA (tRNA) delivers the correct amino acid to the ribosome based on the mRNA codon sequence. Enzymes called aminoacyl-tRNA synthetases attach specific amino acids to tRNA molecules at their attachment sites. The anticodon sequence at the other end of tRNA ensures the correct amino acid reaches the ribosome, allowing the growing polypeptide chain to be built with the proper amino acid sequence.

After a peptide bond forms between two amino acids, the ribosome moves forward to the next codon in the mRNA sequence. This forward movement is called translocation and continues codon by codon until the ribosome encounters a stop codon. Translocation positions each successive tRNA-amino acid complex in the correct location for the next peptide bond formation.

Stop codons do not have corresponding tRNAs. Instead, proteins called release factors bind to the stop codon, triggering the ribosome to release the newly synthesized protein. This causes the ribosome to dissociate from the mRNA, completing the translation process and termination of translation.

Some tRNA molecules can bind to more than one codon sequence, enabling coding versatility known as the wobble effect. This occurs because tRNA molecules have lower binding specificity to the third nucleotide in the mRNA codon compared to the first two nucleotides. This flexibility allows cells to use fewer tRNA types while still accurately translating all 20 amino acids.

Mutations affecting any part of the translation machinery can cause disease. For example, hyperferritinemia results from mutations in the five prime untranslated region of mRNA, causing abnormally high translation rates of the iron protein ferritin, which accumulates in tissues and causes cloudy eye lenses. Diamond-Blackfan anemia stems from mutations in the RPS19 gene, a component of the small ribosomal subunit.

In eukaryotes, translation occurs in the cytoplasm or on the rough endoplasmic reticulum after mRNA is transported from the nucleus. In prokaryotes, which lack a nucleus, translation occurs in the cytoplasm while mRNA is still being transcribed. This difference reflects the compartmentalization of gene expression in eukaryotic cells versus the coupled transcription-translation in prokaryotes.