A codon represents a sequence of three nucleotides on a messenger RNA (mRNA) molecule that specifies a particular amino acid or signals the end of protein production. The start codon, nearly universally represented by the sequence AUG, functions as the dedicated signal that marks the precise beginning of the protein-building process, known as translation. This genetic “on switch” is recognized by the cellular machinery responsible for synthesizing proteins from the genetic blueprint carried by the mRNA. The start codon’s primary function is to direct the machinery to the exact point where the linear sequence of amino acids should begin. Its consistent presence ensures that the genetic information is correctly interpreted and converted into a functional protein.
The Physical Position on the Messenger RNA Strand
The start codon is positioned at the beginning of the coding sequence (CDS), the section of the mRNA that contains the instructions for the protein’s amino acid chain. It serves as the physical boundary between the non-coding and coding parts of the transcript. Directly preceding the start codon is the 5′ Untranslated Region (5′ UTR), a segment of the mRNA that is transcribed from the DNA but is not translated into protein. The start codon is the first triplet of the CDS, and its location dictates where the ribosome begins linking amino acids together.
Once the ribosome locates this initial AUG, it establishes the precise reading frame for the rest of the message. Every subsequent codon is read in a non-overlapping triplet sequence starting from this point. The physical placement of the start codon on the mRNA strand is therefore a fundamental determinant of the final protein product.
Regulatory Sequences That Identify the Start Site
Simply containing the AUG sequence is not enough for an mRNA to begin translation, as AUG triplets can occur many times throughout the coding sequence, where they simply code for the amino acid Methionine. The cellular machinery needs contextual information, which is provided by specialized regulatory sequences that surround the true start codon. These sequences act as identifiers, ensuring the ribosome initiates protein synthesis at the correct location.
Prokaryotic Identification
In prokaryotic organisms, such as bacteria, this identifier is the Shine-Dalgarno sequence, a purine-rich region typically found three to ten nucleotides upstream of the AUG start codon. This sequence is recognized by the 16S ribosomal RNA component of the small ribosomal subunit, which helps position the ribosome on the mRNA transcript. The interaction between the Shine-Dalgarno sequence and the ribosome precisely aligns the initiation machinery over the start codon.
Eukaryotic Identification
Eukaryotic organisms, including humans, employ the Kozak consensus sequence, which spans and surrounds the AUG start codon. The ideal Kozak sequence has the consensus structure GCC(A/G)CCAUGG, with the AUG triplet embedded within it. Strong translational contexts are defined by the presence of a purine (A or G) at the -3 position and a guanine (G) at the +4 position of the AUG. The Kozak sequence facilitates recognition of the correct start codon by the small ribosomal subunit as it scans the mRNA, influencing the efficiency of translation initiation.
The Role of the Start Codon in Translation Initiation
Once the regulatory sequences guide the ribosome to the correct location, the start codon triggers translation initiation. This process involves the binding of a specific transfer RNA (tRNA) that recognizes the AUG sequence. This specialized initiator tRNA carries the amino acid Methionine in eukaryotes and archaea, or N-formylmethionine (fMet) in bacteria.
The small ribosomal subunit, along with initiation factors, binds to the mRNA and scans the 5′ UTR until it encounters the start codon within the proper context. When the initiator tRNA successfully base-pairs its anticodon (UAC) with the AUG start codon, the process pauses, confirming the correct starting position. Initiation factors are then released, signaling the recruitment of the large ribosomal subunit. The large subunit binds to the small subunit, forming a complete, functional ribosome. The initiator tRNA is positioned in the P (peptidyl) site, ready to begin the elongation phase of protein production.
The Importance of Reading Frames
The precise identification of the AUG start codon is paramount because it establishes the Open Reading Frame (ORF), the sequence of codons that will be translated into a functional protein. Genetic information is read sequentially in non-overlapping triplets, and the start codon dictates where this reading must begin. Once the ribosome locks onto the AUG, it defines one of three possible reading frames for the entire coding sequence. If the ribosome begins reading just one or two nucleotides off the true start codon, it results in a shift of the reading frame, known as a frameshift. This error changes every subsequent codon, leading to a completely different sequence of amino acids and usually resulting in a non-functional protein.