From DNA to Protein

In short: Protein synthesis is how a cell uses a gene to make a protein. In transcription, the gene is copied into mRNA in the nucleus, and in translation, a ribosome reads the mRNA three bases (a codon) at a time and joins the matching amino acids into a polypeptide.

Starting point: what you already know

DNA is a double helix with bases A, T, C and G (see the previous chapter).
Ribosomes make proteins (see Cell Organelles).
Enzymes and many hormones are proteins.

Genes, proteins and RNA

A gene is a section of DNA that codes for a polypeptide (a chain of amino acids, which folds into a protein). There are 20 different amino acids, and the order of bases in the gene sets the order of amino acids.

RNA is a single-stranded copy molecule. It differs from DNA:

	DNA	RNA
Strands	Double	Single
Sugar	Deoxyribose	Ribose
Bases	A, T, C, G	A, U (uracil), C, G
Where	Nucleus (and mitochondria, chloroplasts)	Made in the nucleus, works in the cytoplasm

Three kinds of RNA help make proteins: mRNA (messenger, the copy), tRNA (transfer, brings amino acids) and rRNA (ribosomal, part of the ribosome).

Step 1: Transcription (in the nucleus)

The DNA double helix unwinds at the gene.
RNA polymerase reads one DNA strand (the template) and builds a matching mRNA strand. In RNA, A pairs with U.
The mRNA leaves the nucleus through a nuclear pore.

Step 2: Translation (at a ribosome)

The ribosome attaches to the mRNA and reads it three bases at a time. Each group of three is a codon.
Each tRNA carries one amino acid and has three bases called an anticodon, which pairs with a codon.
The ribosome joins the amino acids with peptide bonds.
A stop codon ends translation, and the polypeptide is released.

From polypeptide to protein

A polypeptide folds into a 3D shape held by bonds between its amino acids. Its shape decides its job. Some proteins are made of more than one polypeptide (haemoglobin has four).

Type of protein	Example
Enzymes	Amylase, DNA polymerase
Structural	Keratin in hair, collagen in skin
Transport	Haemoglobin, membrane channels
Hormones	Insulin
Defence	Antibodies

DNA to protein

Gene

Codes for a polypeptide
Base order sets amino acid order

RNA

Single strand
Uracil instead of thymine
mRNA, tRNA, rRNA

Transcription

In nucleus
RNA polymerase makes mRNA

Translation

At ribosome
Codon and anticodon
Peptide bonds
Stop codon

Code

Triplet
Universal
Degenerate

Year 11Processing and gene expression

In eukaryotes, the first mRNA copy contains introns (non-coding sections) and exons (coding sections). Before leaving the nucleus, the introns are cut out and the exons joined (splicing). A cap and a tail are added to protect the mRNA. Different splicing of the same gene can make different proteins, so humans make far more than 20 000 kinds of protein from about 20 000 genes.

Every cell has the same genes, but only some are expressed (switched on). Promoters and transcription factors (proteins that bind DNA) control when a gene is transcribed. Environmental factors like temperature, diet and stress can affect expression too. Siamese cats have dark fur on their cooler ears and paws because their pigment enzyme only works at lower temperatures.

Strands and anticodons. The mRNA is complementary to the template strand, so it has the same sequence as the coding strand, with U for T. Coding strand ATG GCA gives mRNA AUG GCA. A tRNA anticodon is complementary to the codon: codon AUG is read by anticodon UAC.

Counting bases. Each amino acid needs three mRNA bases, so 150 amino acids need at least $150 \times 3 = 450$ bases (plus 3 for the stop codon). If a gene is 1200 bases with introns of 400 and 250 bases, the mature mRNA has $1200 - 650 = 550$ bases.

Same protein, different genes. Because the code is degenerate, two slightly different insulin genes can still code for exactly the same amino acids.

Environment and phenotype. Hydrangeas of one genotype are blue in acid soil and pink in alkaline soil. Himalayan rabbits, like Siamese cats, have black fur only on cooler parts (ears, nose, feet, tail), where their pigment enzyme can work.

Year 12Epigenetics

Epigenetics is change in gene expression that does not change the DNA sequence. Chemical tags such as methyl groups on DNA, or changes to how tightly DNA is wound on histones, switch genes off or on. Some tags can be passed from cell to cell and even, in some cases, to offspring. Honeybee larvae fed royal jelly become queens rather than workers, even though their DNA is the same, because of epigenetic changes.

Levels of protein structure. The amino acid order is the primary structure. Folding into coils and sheets is secondary. The full 3D shape is tertiary. Several polypeptides joined together, like the four chains of haemoglobin, is quaternary structure.

Shape is everything. An enzyme's active site fits its substrate exactly. Changing one amino acid there can change the shape so the substrate no longer fits, and the enzyme stops working.

Cracking the code. In 1961 Nirenberg added mRNA made only of uracil (UUU UUU ...) to a cell-free system and got a chain of only phenylalanine. This showed that UUU codes for phenylalanine and that the code is read in triplets.

One faulty tRNA, many proteins. If the anticodon of a tRNA changes, it puts the wrong amino acid in at that codon in every protein the cell makes.

Quick summary

A gene codes for a polypeptide. The base order sets the amino acid order.
Transcription in the nucleus: RNA polymerase copies a gene into mRNA (U replaces T).
Translation at a ribosome: codons on mRNA pair with tRNA anticodons, and amino acids are joined by peptide bonds.
The code is triplet, universal and degenerate, with start (AUG) and stop codons.
Protein shape decides function. Gene expression is controlled, so cells make different proteins.

Quiz

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Which base is in RNA but not DNA?
1. A Thymine
2. B Uracil
3. C Adenine
4. D Guanine
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B: Uracil
RNA has uracil in place of thymine.
Where does transcription happen in a eukaryotic cell?
1. A The nucleus
2. B The ribosome
3. C The cell membrane
4. D The Golgi body
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A: The nucleus
DNA is copied into mRNA in the nucleus.
Where does translation happen?
1. A The nucleus
2. B At ribosomes
3. C In the vacuole
4. D In lysosomes
Show answer
B: At ribosomes
Ribosomes read mRNA and build polypeptides.