Protein synthesis is the process of translating genetic blueprints into functional proteins. For this translation to be accurate, it must begin at a precise, predetermined location on the genetic script. This specific starting point ensures the genetic message is read in the correct sequence from the beginning. Without a clear signal to initiate the process, cellular machinery could start at random, leading to the assembly of incorrect proteins.
Defining the Start Codon
Genetic information is transcribed from DNA into a messenger RNA (mRNA) molecule, which is read by cellular machinery. This message is arranged in three-nucleotide units called codons, with each codon corresponding to a specific amino acid. Among these units, one serves as the primary initiation signal for protein synthesis and is known as the start codon.
The most common start codon across nearly all life is AUG. It functions as the marker on the mRNA sequence that tells the ribosome where to begin assembling a protein chain. The start codon also establishes the “reading frame,” ensuring all subsequent codons are read correctly in groups of three.
The Initiator Amino Acid
The start codon AUG has a dual function: it signals the beginning of translation and codes for a specific amino acid. In eukaryotes, such as plants and animals, the AUG codon directs the incorporation of the amino acid methionine. Therefore, methionine is the first amino acid in all newly synthesized polypeptide chains in these organisms.
In prokaryotic organisms like bacteria, the process is slightly different. The AUG start codon codes for a modified version of methionine called N-formylmethionine (fMet). The formyl group marks it as the first amino acid, distinguishing it from other methionine residues in the protein sequence. This initial amino acid, whether methionine or fMet, is often removed by enzymes after translation, so it may not be present in the final protein.
Mechanism of Translation Initiation
Translation begins when the small subunit of a ribosome binds to the mRNA molecule and scans it for the AUG start codon. Once the start codon is located, an initiator transfer RNA (tRNA) molecule carrying the appropriate amino acid is recruited.
This initiator tRNA has an anticodon, a complementary three-nucleotide sequence, that binds to the AUG start codon on the mRNA. Following this binding, the large ribosomal subunit joins the complex to form a functional ribosome. The initiator tRNA is positioned in the P-site, ready for the next amino acid to arrive and begin the elongation of the polypeptide chain.
Variations in Start Codons
While AUG is the most common signal for translation initiation, it is not the only one. In prokaryotes, codons such as GUG and UUG can sometimes function as start codons, though less frequently than AUG. When these alternative codons act as the starting signal, a specialized initiator tRNA ensures the insertion of methionine or fMet as the first amino acid.
In eukaryotes, non-AUG start codons are much rarer but do occur. For example, the CUG codon, which normally codes for leucine, can occasionally initiate translation in some mammalian cells. Mutations that alter the standard AUG start codon can prevent the protein from being made. In other cases, the cell’s machinery might use a different, downstream start codon, leading to a truncated and often non-functional protein.