Protein synthesis: how a gene becomes a protein

How to use this simulation

1. Press play and watch Stage 1. RNA polymerase slides along the template strand and builds the mRNA one base at a time. Check that every mRNA base is the partner of the template base above it, and that the mRNA matches the coding strand with U in place of T.
2. Keep watching into Stage 2. The mRNA leaves the nucleus, the ribosome scans for the first AUG, the Met tRNA arrives, and then one tRNA at a time delivers an amino acid. The codon being read lights up in the genetic code table under the animation.
3. Drag the step slider to scrub backwards and forwards. Dragging pauses the animation, so you can stop on the exact moment a peptide bond forms or a stop codon is read.
4. Switch the gene between the three samples, or choose Type your own and enter any string of A, T, G and C. If your sequence has no ATG, the ribosome scans to the end and nothing is made.
5. Tick the mutation box, choose a position and a new base, and read the Effect of the mutation line. Try position 22 and the base T on sample 2 to see the sickle-cell change.
6. Use the readings panel to follow bases transcribed, the codon being read, its anticodon, the number of amino acids in the chain and the finished protein.

Your cells are following a recipe right now

A hair grows about a centimetre a month. That hair is mostly a protein called keratin, and your body is making it from scratch, out of loose amino acids, as you read this sentence. The same thing is happening with the enzymes that digest your lunch, the haemoglobin in your blood, the insulin that controls your blood sugar and the antibodies that fought off your last cold.

Every one of those proteins has a recipe, and the recipe is a gene. Your DNA is a library of recipes. But the library never leaves its building (the nucleus), and a recipe book is useless if nobody can cook from it. So the cell does what a sensible cook does: it photocopies one recipe, carries the copy to the kitchen, and builds the dish there.

That is the whole story of this page. The photocopy is called mRNA, and making it is called transcription. The kitchen is the ribosome, and cooking is called translation. In the simulation above you can watch both stages on a short gene, change a letter of the recipe, and see exactly what that does to the dish.

From zero: the central dogma in plain words

DNA is a long string of four letters: A, T, G and C. A gene is a stretch of that string that holds the instructions for one product, usually a protein. A protein is a chain of amino acids folded into a working shape, and there are twenty kinds of amino acid to choose from.

So the cell has a translation problem. DNA is written in four letters, proteins are written in twenty. The solution is the genetic code: groups of three letters, called codons, each stand for one amino acid. With three letters from a four-letter alphabet there are 64 possible codons, which is plenty for 20 amino acids plus a "stop" signal.

The direction of information flow is summed up by the central dogma of molecular biology: DNA → RNA → protein. DNA is transcribed into RNA, and RNA is translated into protein. (Some viruses and a few lab techniques copy information backwards from RNA to DNA, but inside your own cells the main road runs one way.)

Two different verbs are hiding in that arrow, and they are easy to mix up. Transcription copies information from one nucleic acid to another, DNA to RNA, in the same "language" of bases, so it is like copying a recipe by hand. Translation changes language, from the four-letter base language to the twenty-letter amino-acid language, so it is like translating the recipe into a dish.

Key words you need before the steps

These words appear in almost every question on this chapter. Read the table once, then come back to it whenever a step uses a word you have forgotten.

Stage 1: transcription, step by step

Transcription happens in the nucleus of a eukaryotic cell (in bacteria, which have no nucleus, it happens in the cytoplasm next to the DNA). Its product is an RNA molecule whose sequence is dictated by the gene. Here are the steps in the order the animation shows them.

The genetic code: a dictionary with 64 words

The genetic code is the rule that turns codons into amino acids. A codon is three bases, so there are 4 × 4 × 4 = 64 codons. Of these, 61 are sense codons that code for an amino acid and 3 are stop codons. The table under the animation is the standard code, and it highlights whichever codon is being read.

How to read the table: find the first base of the codon in the left column, the second base along the top, and then the third base among the four lines inside the cell. For example, AUG is row A, column U, third line G, and it says Met.

Here are the properties that every exam asks about.

• It is a triplet code: three bases make one codon.
• It is degenerate (redundant): most amino acids have more than one codon. Leu, Ser and Arg have 3 each, while Met and Trp have only one.
• It is unambiguous: a given codon always means the same amino acid, never two different ones.
• It is non-overlapping and has no punctuation: the message is read three bases at a time from a fixed starting point, with no gaps.
• It has a start and stops: AUG starts translation (and codes for Met), while UAA, UAG and UGA end it.
• It is almost universal: bacteria, plants and humans use the same table, with only small exceptions such as in mitochondria. That is why a human gene can work in a bacterium.

Stage 2: translation, step by step

Translation happens on ribosomes in the cytoplasm. The ribosome has two parts, a small subunit and a large subunit. Between them sit three docking sites for tRNA: the A site (aminoacyl, where a new tRNA arrives), the P site (peptidyl, which holds the tRNA attached to the growing chain) and the E site (exit). The animation labels the P and A sites on the ribosome.

Mutations: what one wrong letter can do

A point mutation swaps one base for another in the gene. Because the code is redundant, the effect on the protein depends on which codon is hit and what it turns into. There are three outcomes that every syllabus names.

• Silent mutation: the new codon codes for the same amino acid, so the protein does not change. Third-base changes are often silent.
• Missense mutation: the new codon codes for a different amino acid, so one residue in the protein is swapped. The protein may work worse, the same or, rarely, better.
• Nonsense mutation: the new codon is a stop codon, so translation ends early and the protein is cut short. It is usually the most damaging.

Try it in the simulation

These experiments take about a minute each. Predict first, then check.

• Let sample 1 run once, start to finish. Write down the mRNA, then the five amino acids, and check them against the readings panel.
• On sample 1, drag the step slider to the first moment the chain contains Met only. How many bases of mRNA were never translated, and why?
• Switch to Type your own and enter CCCGGGAAATTT. The mRNA has no AUG. What does the ribosome do, and what does the readings panel say?
• Enter ATGAAATTTGGG with no stop codon. The chain is built, but the status reads that no stop codon was found. In a real cell what would go wrong?
• On sample 2 tick the mutation box and set the position to 22 and the base to T. Read the effect line. Then try position 23 with A and position 21 with T and compare the three.
• On sample 3, find the two Leu residues in the chain and read which codon each one came from. Same amino acid, different codons: that is degeneracy on screen.
• On sample 1 mutate the base at position 6 to T and watch the chain stop after Met. The effect line calls it a nonsense change.

Solved problems, computed from the same code as the simulation

Every sequence and every count below is produced by the same code table that drives the animation, so the answers cannot drift out of step with it.

Common mistakes (and how to avoid them)

Each of these costs marks every year. Learn the fix, not just the fault.

• Writing the template instead of the coding strand for the mRNA. Fix: the mRNA matches the coding strand (T becomes U) and pairs with the template.
• Leaving T in an RNA sequence. Fix: RNA never contains T, so write U everywhere.
• Reading a template written 5′→3′ without reversing it. Fix: reverse first, then pair.
• Starting to read codons from the first base of the mRNA. Fix: scan for the first AUG and start there. Bases before it are not translated.
• Counting the stop codon as an amino acid. Fix: amino acids = codons − 1 when a stop is present.
• Mixing up codon and anticodon. Fix: the codon is on the mRNA, the anticodon is on the tRNA, and they pair.
• Saying the tRNA carries the codon. Fix: it carries an anticodon and an amino acid.
• Thinking a silent mutation changes nothing at all. Fix: the DNA changed, but the protein did not.

Where this shows up in real life

Protein synthesis is not just a chapter. It is the target and the tool of a lot of modern medicine and technology.

Exam corner (general)

Questions on this topic follow a few predictable shapes. For long answers, structure your writing as numbered steps and label every strand 5′ and 3′.

• Define transcription, translation, codon and anticodon (1 or 2 marks each).
• Given a DNA strand, write the mRNA and the amino-acid sequence using the codon table (the most common calculation).
• Describe the steps of transcription or translation, usually in 4 to 6 numbered points.
• Compare DNA and RNA, or mRNA, tRNA and rRNA, in a table.
• State the features of the genetic code (triplet, degenerate, unambiguous, non-overlapping, nearly universal).
• Classify a given mutation as silent, missense or nonsense and justify it from the codons.

Revision summary

Read this the night before the exam.

• Central dogma: DNA → RNA → protein.
• Transcription: RNA polymerase reads the template 3′→5′ and builds mRNA 5′→3′, pairing A–U, T–A, G–C, C–G.
• The mRNA has the same sequence as the coding strand, with U in place of T.
• Eukaryotic pre-mRNA gets a cap, a poly-A tail and splicing before it leaves the nucleus.
• The code has 64 codons: 61 for amino acids, 3 stops. AUG is both the start and Met.
• tRNA brings the amino acid and pairs through its anticodon.
• Translation: initiation (find AUG), elongation (arrive, bond, shift), termination (stop codon and release factor).
• Silent, missense and nonsense describe what a point mutation does to the protein.

Frequently asked questions