What Is Protein Synthesis? How Cells Build Proteins

DNA stores instructions in the order of its bases, but the DNA itself usually stays protected inside the nucleus of a eukaryotic cell. When a cell needs to use a gene, an enzyme reads one DNA strand and builds a matching molecule of messenger RNA, or mRNA. This first stage is transcription. The mRNA carries a temporary copy of the useful genetic message, so the cell can use the information without moving the original DNA out of its main storage place.

To understand what protein synthesis is, focus on the idea of copying before building. During transcription, RNA bases pair with exposed DNA bases according to complementary rules. The finished RNA message is processed in eukaryotic cells, then leaves the nucleus through a pore. It travels into the cytoplasm, where ribosomes can read it. A ribosome does not read the whole message as one long word. It reads the mRNA in groups of three bases called codons.

Each codon helps specify an amino acid or a start or stop instruction. Because the order of codons comes from the gene, changing the DNA sequence can sometimes change the amino acid sequence in the finished protein. Not every DNA change has that effect, but the connection explains why genetic information can influence cell structure and function.

Translation is the second major stage of protein synthesis. A ribosome attaches to the mRNA and moves along its codons. Transfer RNA, or tRNA, molecules carry amino acids to the ribosome. Each tRNA has an anticodon that can pair with a matching mRNA codon. This pairing helps place the correct amino acid next in the growing chain.

The ribosome joins amino acids with peptide bonds, one after another. The chain keeps growing until the ribosome reaches a stop codon. Then the new polypeptide is released. It may fold into a specific three-dimensional shape, join with other chains, or be chemically modified before it becomes a working protein. Protein shape matters because enzymes, receptors, antibodies, and structural proteins all depend on precise shapes to do their jobs.

A simple way to remember transcription and translation is to ask where the information is going. Transcription moves the message from DNA into RNA. Translation changes the language of nucleic acid bases into the language of amino acids. That shift is the heart of protein synthesis. Keeping those two stages separate also helps you explain where each molecule enters the process.

When you revise protein synthesis, keep the steps in one calm chain:

• •DNA contains a gene with the instructions for a protein.
• •Transcription makes an mRNA copy of that gene.
• •The mRNA travels to a ribosome in the cytoplasm.
• •tRNA brings amino acids that match the mRNA codons.
• •The ribosome links the amino acids, and the new chain folds into a protein.

Sickle cell anaemia shows the path from gene to protein in a single step. The gene for beta globin, one of the chains in haemoglobin, normally contains the DNA triplet GAG at the position for the sixth amino acid. In the sickle cell version, one base has changed, giving GTG. After transcription, the mRNA codon becomes GUG instead of GAG, and during translation the ribosome adds the amino acid valine where glutamic acid should be. Every other amino acid in the chain is unchanged, yet this one swap alters how the finished haemoglobin behaves.

Glutamic acid carries an electric charge and mixes well with water, while valine does not. When oxygen levels are low, the altered haemoglobin molecules can stick together into long fibres that distort red blood cells into a curved sickle shape. Those cells can block small blood vessels and break down early. Not every base change has such an effect, because the genetic code has 64 codons for only 20 amino acids plus stop signals, so several codons often specify the same amino acid. A change that leaves the amino acid the same is called a silent mutation.

For years after the structure of DNA was described in 1953, nobody knew which codons stood for which amino acids. The first breakthrough came in 1961, when Marshall Nirenberg and Heinrich Matthaei added an artificial RNA made only of uracil bases to a mixture taken from broken-open bacterial cells. The mixture contained ribosomes, tRNA and amino acids, and it made a chain consisting only of phenylalanine. So UUU had to code for phenylalanine. Over the next few years, Nirenberg, Har Gobind Khorana and others used similar experiments with different synthetic messages to work out what all 64 codons do.

One of the most important findings was that the code is almost universal. Bacteria, plants and people read nearly all codons the same way, which is strong evidence that all life shares a common ancestor. It also makes biotechnology possible. Because bacteria can read a human gene, they can be engineered to make human proteins, and human insulin produced this way went on sale in the early 1980s, replacing much of the insulin extracted from pigs and cattle. There are small exceptions to the code. In human mitochondria, for example, the codon UGA codes for the amino acid tryptophan instead of acting as a stop signal.

Many antibiotics work by attacking protein synthesis, exploiting small differences between bacterial ribosomes and our own. Bacterial ribosomes are smaller, described as 70S, while those in the cytoplasm of human cells are 80S, the S standing for a measure of how fast they settle in a centrifuge. Different drugs block different steps. Tetracyclines stop incoming tRNA from binding properly to the ribosome. Macrolides such as erythromycin lodge in the tunnel through which the growing protein chain leaves the ribosome. Aminoglycosides such as streptomycin make the ribosome misread codons, so faulty proteins are built. In each case the bacterium can no longer make the proteins it needs.

The differences are not perfect, which explains some side effects. Mitochondria descend from bacteria taken into early cells, and their ribosomes still resemble bacterial ones. Aminoglycosides can damage hearing, and people who carry a particular variant in their mitochondrial ribosomal RNA are especially sensitive, because the change makes their mitochondrial ribosomes even more bacteria-like. Detailed knowledge of how these drugs fit the ribosome came from mapping its structure atom by atom, work for which Venkatraman Ramakrishnan, Thomas Steitz and Ada Yonath shared the 2009 Nobel Prize in Chemistry. Their maps now help chemists design antibiotics that get around bacterial resistance.

Protein synthesis is the route from genetic instructions to a working chain of amino acids. Transcription copies a gene into mRNA, and translation uses ribosomes and tRNA to assemble the protein. If you remember DNA to mRNA to ribosome to amino acid chain, you have the main story.