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From gene to protein
Why proteins matter, how RNA differs from DNA, transcription of a gene into mRNA, the triplet genetic code and how it was cracked, translation by ribosomes and tRNA, and how mRNA vaccines use the same process.
Your hair, the enzymes digesting your lunch, the haemoglobin carrying oxygen, the antibodies fighting a cold: all proteins, and all built from the same 20 building blocks strung together in different orders. DNA's only job is to store the order. Right now, each of your cells is making thousands of proteins a second by reading it.
Why proteins?
A protein is a long chain of amino acids, usually hundreds long, folded into a precise 3D shape. Twenty different amino acids are used, and the order they are joined in (the protein's sequence) decides how the chain folds, and so what the protein can do. Proteins do almost every job in a cell:
- enzymes speed up chemical reactions (amylase digests starch)
- structural proteins build tissues (keratin in hair, collagen in skin and bone)
- transport proteins carry substances (haemoglobin carries oxygen)
- hormones and receptors carry and receive signals (insulin)
- antibodies recognise invaders (Year 9, 4I).
Your genes control your characteristics mainly by deciding which proteins your cells make. Brown eyes, for example, contain lots of the pigment melanin, made by a chain of enzymes. So the path from gene to trait is: DNA → RNA → protein → characteristic.
RNA: the working copy
DNA stays safely inside the nucleus, but proteins are made on ribosomes in the cytoplasm. The cell sends out copies of the gene instead, made of RNA (ribonucleic acid). RNA differs from DNA in three ways:
| DNA | RNA | |
|---|---|---|
| Strands | Two (double helix) | One |
| Sugar | Deoxyribose | Ribose |
| Bases | A, T, G, C | A, U (uracil), G, C |
| Where | Nucleus (and mitochondria) | Made in the nucleus, works mostly in the cytoplasm |
| Lifetime | Permanent | Minutes to hours, then broken down |
Three kinds of RNA work together: messenger RNA (mRNA) carries the copy of the gene; transfer RNA (tRNA) brings amino acids to the ribosome; and ribosomal RNA forms the core of the ribosome itself.
Protein synthesis in two stages
1 Transcription (in the nucleus). The DNA unzips along the length of one gene. The enzyme RNA polymerase moves along one strand, the template strand, and builds a matching strand of mRNA using the base-pairing rules, except that RNA uses U wherever DNA would have T. So template DNA TAC becomes mRNA AUG. The mRNA peels away, the DNA zips back up, and the mRNA leaves the nucleus through a nuclear pore.
2 Translation (in the cytoplasm). A ribosome clamps onto the mRNA and reads its bases three at a time. Each group of three bases is a codon, and each codon stands for one amino acid. Translation always starts at the codon AUG. Each tRNA molecule carries one particular amino acid at one end and has three bases called an anticodon at the other. When a tRNA's anticodon pairs with the codon on the mRNA, the ribosome joins its amino acid to the growing chain, then shifts along one codon. This continues until the ribosome reaches a stop codon (UAA, UAG or UGA), which has no tRNA. The finished chain is released and folds into its shape.
A ribosome adds roughly 5 to 20 amino acids a second, and many ribosomes can read the same mRNA one after another, so one gene can be turned into thousands of copies of a protein.
The genetic code
With four bases, codons of one base could code for only 4 amino acids and codons of two bases only 16. Three bases give 4 × 4 × 4 = 64 codons, more than enough for 20 amino acids. 61 codons code for amino acids and 3 are stop signals. Most amino acids have more than one codon: the code is redundant.
Cracking it took five years. In 1961 Marshall Nirenberg and Heinrich Matthaei made artificial mRNA that was just a string of U bases, added it to cell extracts, and found it produced a chain made only of the amino acid phenylalanine. So UUU means phenylalanine. Teams led by Nirenberg, Har Gobind Khorana and others tested every combination, and by 1966 all 64 codons were known. The code is almost universal: the same codons mean the same amino acids in bacteria, plants, kangaroos and you. That is strong evidence that all life shares a common ancestor, and it is why a human gene put into a bacterium makes a human protein (1J).
The table shows all 64 mRNA codons. Find the first base on the left, then the column for the second base.
| 1st base | 2nd base U | 2nd base C | 2nd base A | 2nd base G |
|---|---|---|---|---|
| U | UUU Phe | UCU Ser | UAU Tyr | UGU Cys |
| UUC Phe | UCC Ser | UAC Tyr | UGC Cys | |
| UUA Leu | UCA Ser | UAA STOP | UGA STOP | |
| UUG Leu | UCG Ser | UAG STOP | UGG Trp | |
| C | CUU Leu | CCU Pro | CAU His | CGU Arg |
| CUC Leu | CCC Pro | CAC His | CGC Arg | |
| CUA Leu | CCA Pro | CAA Gln | CGA Arg | |
| CUG Leu | CCG Pro | CAG Gln | CGG Arg | |
| A | AUU Ile | ACU Thr | AAU Asn | AGU Ser |
| AUC Ile | ACC Thr | AAC Asn | AGC Ser | |
| AUA Ile | ACA Thr | AAA Lys | AGA Arg | |
| AUG Met (start) | ACG Thr | AAG Lys | AGG Arg | |
| G | GUU Val | GCU Ala | GAU Asp | GGU Gly |
| GUC Val | GCC Ala | GAC Asp | GGC Gly | |
| GUA Val | GCA Ala | GAA Glu | GGA Gly | |
| GUG Val | GCG Ala | GAG Glu | GGG Gly |
The template strand of a short piece of DNA reads TAC GGA TTC ATT. What mRNA is made, and what is the chain of amino acids?
Pair each base, using U instead of T: T→A, A→U, C→G, G→C. The mRNA is AUG CCU AAG UAA.
Look up each codon: AUG = Met (start), CCU = Pro, AAG = Lys, UAA = stop.
The chain is Met–Pro–Lys, and translation stops at UAA.
- Choose the haemoglobin gene. Transcribe it, then translate it one codon at a time. Check each amino acid against the codon table.
- Look at the mRNA and the DNA template strand. Which mRNA base pairs with an A on the template?
- Run the mini gene to the end. What happens at the STOP codon?
- Try "Find the start". How many bases are skipped before translation begins, and why?
mRNA vaccines
In 2020 the first mRNA vaccines were used against COVID-19. They contain mRNA for the virus's spike protein, wrapped in a tiny bubble of fat so it can enter cells. Your ribosomes translate it, exactly as above, and make harmless copies of the spike protein, which your immune system learns to recognise. The mRNA never enters the nucleus, cannot change your DNA, and is broken down within days, as all mRNA is. Hungarian-American biochemist Katalin Karikó and American immunologist Drew Weissman shared the 2023 Nobel Prize in Physiology or Medicine for discovering how to modify mRNA so the body does not destroy it before it can be read. Researchers are now testing mRNA vaccines and treatments for cancers, influenza and other diseases.
Test yourself
Where does transcription take place in a human cell?
The DNA template is in the nucleus, so mRNA is made there.
A DNA template strand reads
GCA. The mRNA codon isG→C, C→G, A→U (RNA has U instead of T).
What is the job of tRNA?
Each tRNA carries one amino acid and has an anticodon that matches a codon.
An mRNA has 300 bases between its start codon and its stop codon (including the start codon, not the stop). How many amino acids are in the protein?
300 ÷ 3 = 100 codons, each one amino acid.
Why does a human insulin gene work when it is put into a bacterium?
The same codons code for the same amino acids in almost all living things.
Label protein synthesis.
Put the steps of protein synthesis in order.
Copying a gene into mRNA is called . RNA contains the base instead of thymine. Each group of three bases on mRNA is a . The matching three bases on a tRNA are the . Proteins are assembled on .
Describe how the information in a gene is used to make a protein. Include the roles of mRNA, tRNA and ribosomes.
The order of bases in a gene codes for the order of amino acids in a protein. In transcription, in the nucleus, the DNA unzips along the gene and RNA polymerase builds a strand of messenger RNA that is complementary to the template strand, with uracil in place of thymine. The mRNA leaves the nucleus through a nuclear pore. In translation, a ribosome in the cytoplasm attaches to the mRNA and reads it one codon (three bases) at a time, starting at AUG. Each transfer RNA carries a particular amino acid and has an anticodon; when its anticodon pairs with the codon, the ribosome joins its amino acid to the growing chain and moves to the next codon. When a stop codon is reached the chain is released and folds into the protein's shape, which determines its function.