Living cells rely on precise instructions, contained within genes, to build proteins. Proteins are molecular machines that perform nearly every cellular task, from catalyzing reactions to providing structural support. The process of converting genetic information into functional proteins begins with transcription, which copies a gene’s DNA sequence into a messenger RNA (mRNA) molecule.
From DNA to Protein: The Essential Steps
The flow of genetic information in biological systems generally follows a path from DNA to RNA to protein, often called the central dogma of molecular biology. DNA, housed within the cell’s nucleus, contains the complete set of genetic instructions. To utilize these instructions, specific DNA segments, known as genes, are first copied into RNA.
This copying process is called transcription, where RNA polymerase reads a DNA template and synthesizes a complementary mRNA molecule. During transcription, DNA unwinds, and RNA polymerase builds an RNA strand by adding nucleotides that pair with the DNA sequence. Once complete, the mRNA molecule detaches from the DNA template and travels into the cell’s cytoplasm.
In the cytoplasm, the mRNA molecule undergoes translation, where its genetic code is read to assemble a specific protein. Ribosomes, the cell’s protein-making machinery, read the mRNA sequence and recruit individual amino acids to form a chain. This chain folds into a precise three-dimensional structure, becoming a functional protein ready to perform its role.
Types of Transcription Errors
While transcription is a precise process, errors can occur during mRNA synthesis. RNA polymerase might occasionally incorporate an incorrect nucleotide. These mistakes result in an mRNA sequence that deviates from the original DNA template.
A common transcription error is a base substitution, where one nucleotide is mistakenly replaced by another. For example, an adenine (A) might be incorporated instead of a guanine (G), or a cytosine (C) replaced by a uracil (U). These are the most frequent transcription errors.
Other errors include insertions, where an extra nucleotide is added, or deletions, where a nucleotide is missed. These insertion and deletion errors, known as indels, can have disruptive consequences. Transcription errors occur at a rate significantly higher than DNA replication errors, with RNA polymerase making approximately one error every 300,000 bases.
How mRNA Errors Alter Protein Production
Errors in the mRNA sequence directly impact protein production, known as translation. During translation, the mRNA sequence is read in three-nucleotide units called codons, each specifying a particular amino acid. A change in even a single nucleotide within an mRNA codon can alter which amino acid is incorporated into the growing protein chain.
A base substitution in the mRNA can lead to a missense mutation, where the altered codon specifies a different amino acid. For example, if a codon that normally codes for alanine is changed due to an error, it might instead code for valine. The impact of such a change depends on the new amino acid and its location within the protein.
Alternatively, a base substitution can result in a nonsense mutation, creating a premature stop codon in the mRNA. Stop codons normally signal the end of protein synthesis. If a transcription error introduces a stop codon too early, it leads to a shortened, or truncated, protein.
Insertions or deletions of nucleotides in the mRNA can cause a frameshift mutation. Because mRNA is read in groups of three, adding or removing nucleotides not in multiples of three shifts the entire reading frame. This alteration changes every subsequent codon, leading to a different sequence of amino acids from that point onward, often resulting in a non-functional protein.
The Impact on Protein Structure and Function
The amino acid sequence of a protein determines its three-dimensional structure, which is related to its function. When transcription errors alter the mRNA sequence, they can lead to changes in the protein’s amino acid composition, affecting its structure and function.
An incorrect amino acid sequence can cause protein misfolding, preventing the protein from achieving its correct three-dimensional shape. A protein’s precise shape is important for its ability to interact with other molecules and perform its specific job.
Misfolded or truncated proteins often result in a loss of function, meaning they can no longer perform their intended cellular tasks. In some cases, the altered protein might retain some activity but with an altered function, working less efficiently or in an unintended manner.
Cells possess quality control mechanisms to identify and manage misfolded or damaged proteins. Severely misfolded or non-functional proteins are often flagged for premature degradation by cellular systems. This breakdown ensures faulty proteins do not accumulate and disrupt cellular processes, but it also means the cell lacks the necessary functional protein. Consequently, the precision of transcription is important because even minor errors can affect a protein’s ability to carry out its function.