Living cells rely on instructions encoded within DNA to carry out their functions. DNA contains the blueprint for life, organized into functional units called genes. These genes hold the information for building proteins. To utilize this genetic information, the cell reads it in specific three-nucleotide units known as codons.
The Primary Start Codon
The cellular machinery recognizes one primary and nearly universal signal to begin protein synthesis: the AUG codon. This triplet consists of adenine (A), uracil (U), and guanine (G). AUG serves as the definitive signal across almost all forms of life, including bacteria, archaea, plants, and animals, indicating where protein synthesis should start. Beyond its role as a starting signal, the AUG codon also codes for a specific amino acid.
In eukaryotes and archaea, AUG specifies the amino acid methionine. In bacteria and in mitochondria, it codes for a modified form called N-formylmethionine (fMet). Consequently, methionine (or fMet) is almost always the first amino acid incorporated into newly synthesized proteins. While methionine can also appear elsewhere within a protein sequence, its presence at the beginning is a direct consequence of the universal AUG start codon.
How Translation Begins
The process of converting the genetic code from messenger RNA (mRNA) into a protein is called translation. This process begins with an initiation phase, where cellular components assemble at the start signal. Ribosomes, which are molecular machines, play a central role in reading the mRNA instructions.
Before protein synthesis can commence, a specialized transfer RNA (tRNA) carrying methionine associates with the small ribosomal subunit. This complex then binds to the mRNA. The ribosome scans along the mRNA until it encounters the AUG start codon. Upon recognizing the AUG, scanning stops, and the larger ribosomal subunit joins. This assembly ensures that protein synthesis initiates at the precise location, establishing the correct reading frame.
Alternative Start Codons
While AUG is the predominant start codon, some exceptions exist where other codons can initiate protein synthesis. These alternative start codons are more common in prokaryotes, like bacteria, than in eukaryotes. Examples include GUG and UUG. In bacteria, non-AUG start codons can initiate translation in approximately 15-20% of genes, with GUG used in about 10-14% and UUG in about 3-8%.
Despite these variations, proteins initiated by alternative start codons still begin with methionine or N-formylmethionine. This occurs because a specialized initiator tRNA carrying methionine recognizes these alternative codons at the beginning of a coding sequence. These alternative start codons represent a nuance in the genetic code, but AUG remains the dominant and universal signal for protein initiation.