Biology • Year 12 • Module 5 • Lesson 10

Transcription — From DNA to mRNA

Build HSC band 5–6 extended-response technique on transcription, real CFTR data, and why eukaryotic cells use a temporary mRNA copy.

Master · Extended Response

1. Extended response with data — CFTR transcript levels in healthy vs ΔF508 cells (Band 5–6)

8 marks   Band 5–6

Stimulus. The CFTR gene codes for the Cystic Fibrosis Transmembrane conductance Regulator, a chloride-ion channel found in airway and intestinal epithelial cells. Around 70% of cystic fibrosis patients of European ancestry carry the ΔF508 mutation — a three-base-pair deletion in the CFTR gene's coding sequence. Trzcińska-Daneluti et al. (2009, Mol Cell Proteomics) measured CFTR mRNA levels in bronchial epithelial cells from healthy donors and from ΔF508 homozygous patients. The data below summarises their results across three independent donor pairs.

Donor pairHealthy CFTR mRNA
(relative units)
ΔF508 CFTR mRNA
(relative units)
% of healthy
11.000.7878%
21.000.8585%
31.000.8181%
Mean1.000.81≈81%

Data adapted from Trzcińska-Daneluti et al. (2009). Mean ΔF508 CFTR mRNA is ~81% of wild-type — i.e. transcription still occurs, but at a modestly reduced level, and the mRNA carries a deletion of three bases.

Q1. Analyse what the data above show about the effect of the ΔF508 mutation on transcription, and evaluate the claim that "if there is still some CFTR mRNA being made, the mutation cannot be acting at the transcription stage." In your response you must:

  • Define transcription and state what a CFTR mRNA molecule carries when it leaves the nucleus.
  • Quote at least one figure from the data table and describe the trend across the three donor pairs.
  • Distinguish between a change in how much mRNA is made and a change in which codons the mRNA carries — and explain which of these the ΔF508 mutation produces.
  • Use the lesson's principle of complementary base pairing to justify why a three-base deletion in the DNA template must change the mRNA at the transcription step, even when overall transcript levels are still ~81% of wild-type.
  • Reach a justified evaluative judgement on the claim.
Stuck? Plan first: define transcription → quote the data → quantity vs codon-content distinction → base-pairing argument → judgement on the claim.

2. Extended response with data — why eukaryotes use mRNA rather than ferrying DNA (Band 5–6)

8 marks   Band 5–6

Stimulus. Different cell types in the human body produce very different amounts of mRNA from particular genes depending on what protein products the cell needs. The data below (adapted from the GTEx Consortium, 2020, Science) shows the relative steady-state level of CFTR mRNA per cell across four tissues. The DNA copy of the CFTR gene is identical in every one of these cells; only the transcription output differs.

0 25 50 75 100 Relative CFTR mRNA level (per cell) 100 83 51 15 Bronchial epithelium Pancreatic duct Sweat gland Skeletal muscle

Figure 2. Relative CFTR mRNA level per cell across four human tissues. Data adapted from the GTEx Consortium (2020), Science.

Q2. Analyse and justify: "Eukaryotic cells use a temporary mRNA copy of each gene rather than ferrying DNA out of the nucleus." Use the figure above to support your reasoning. In your response you must:

  • Define mRNA as a temporary, portable copy of a gene's coded information and identify what produces it.
  • Use at least two specific data points from Figure 2 to show that the same gene can produce very different amounts of mRNA in different tissues.
  • Explain at least two biological reasons why moving the DNA itself out of the nucleus each time a protein is needed would be a poor strategy (e.g. damage / mutation risk, only one copy per cell, need for many simultaneous protein products).
  • Link the lesson's point that mRNA preserves codon information through complementary base pairing — so the information that reaches the ribosome is faithful to the gene without exposing the gene itself.
  • Reach a justified judgement on why a temporary mRNA copy is the more effective strategy across the cell types shown.
Stuck? Use Card 3 (why mRNA is temporary) as your spine, then attach Card 2 (template + base pairing) as your information-faithfulness argument.
Answers — Do not peek before attempting

Q1 — Sample Band 6 response (8 marks), annotated

Transcription is the process of producing an mRNA copy from a DNA template strand, with RNA nucleotides pairing complementarily with the exposed template bases (A–U, T–A, C–G, G–C). The mRNA that leaves the nucleus carries the gene's coded sequence as a series of three-base codons. [1 — defines transcription and identifies what mRNA carries]

The data show that ΔF508 patients still produce CFTR mRNA, but at a modestly reduced level: 78%, 85% and 81% of healthy wild-type across the three donor pairs, with a mean of about 81% of wild-type. The trend is consistent across all three pairs — ΔF508 mRNA is always present and always slightly lower than healthy. [1 — quotes data and describes trend]

However, "how much" mRNA is produced is a separate question from "which codons" the mRNA carries. The ΔF508 mutation is a three-base-pair deletion in the DNA coding sequence — the template strand has three bases missing at one location. [1 — distinguishes quantity from codon content; identifies which the mutation produces]

Because transcription works by complementary base pairing of RNA nucleotides to the exposed template, the mRNA built from a template missing three bases must also be missing the matching three RNA bases. The mRNA therefore carries one fewer codon (and a possible boundary shift) compared with wild-type mRNA — its sequence of codons is altered at the transcription step, before translation begins. [1 — applies complementary base pairing to justify the codon change at transcription]

So the claim that "if there is still mRNA being made, the mutation cannot be acting at transcription" is flawed. It treats transcription as if it only affected mRNA quantity, when in fact transcription is the step that copies the base sequence — including any deletion — into the mRNA. [1 — directly addresses the flaw in the claim's logic]

The 81% figure tells us about the rate or stability of CFTR transcription, while the deletion itself acts on the content of every mRNA produced. Both effects are real, and both originate in the transcription step. [1 — integrates the two effects and locates both at transcription]

This is consistent with the lesson's framing that the CFTR DNA sequence determines, by complementary pairing, the codon sequence of every CFTR mRNA leaving the nucleus. [1 — uses precise lesson terminology, links back to Card 2]

Final judgement: the claim is rejected. The ΔF508 mutation acts at the transcription step in two distinguishable ways — it reduces transcript level to about 81% of wild-type, and it changes the codon content of every CFTR mRNA produced. Either effect alone would be enough to refute the claim; the data show both. [1 — justified evaluative judgement]

Marking summary (out of 8): 1 — transcription definition + mRNA carries codons; 1 — data quoted and trend described; 1 — quantity vs codon-content distinction with identification; 1 — base-pairing argument for codon change; 1 — addresses the flaw in the claim's logic; 1 — integrates quantity and content effects at transcription; 1 — precise lesson terminology throughout; 1 — explicit justified judgement on the claim.

Q2 — Sample Band 6 response (8 marks), annotated

mRNA is a temporary, portable RNA copy of a gene's coded information, produced during transcription by complementary base pairing of RNA nucleotides to a DNA template strand. Its purpose is to carry the gene's codon sequence away from the DNA without the DNA itself having to move. [1 — defines mRNA and identifies what produces it]

Figure 2 shows that the same CFTR gene — present in every cell at identical DNA copy number — gives very different mRNA levels across tissues. Bronchial epithelium has 100 relative units, pancreatic duct cells have 83, sweat gland 51 and skeletal muscle only 15. [1 — uses at least two specific data points to show same-gene-different-mRNA]

If the cell had to ferry the actual DNA copy of CFTR to the ribosome to produce CFTR protein, several problems would follow. First, there is essentially one copy of each gene per nucleus (two in diploid cells) — that DNA cannot be in two places at once, but bronchial epithelial cells need a constant supply of CFTR protein to maintain mucus hydration. Many simultaneous protein products would compete for a single DNA copy. [1 — reason 1: single DNA copy can't supply many simultaneous needs]

Second, DNA is the cell's permanent hereditary store. Repeatedly exposing it to cytoplasmic enzymes, mechanical movement, and reactive molecules during transport would accumulate damage and mutations across the cell's lifetime. mRNA, in contrast, is expendable — a damaged transcript can simply be degraded and another made. [1 — reason 2: damage and mutation risk to permanent DNA]

Third, transcription lets the cell amplify the message. From one CFTR gene, a bronchial cell can produce many CFTR mRNA molecules, each of which can be translated multiple times. This is why bronchial epithelium can sustain ~100 units of CFTR mRNA from the same gene that produces only 15 units in muscle — transcription rate is the regulator, not DNA copy number. [1 — uses the data to show tissue-specific amplification — connects to figure quantitatively]

The mRNA strategy also preserves information faithfully. Complementary base pairing (A–U, T–A, C–G, G–C) guarantees that the mRNA's codon sequence is determined by the gene's template-strand base sequence, so the message that reaches the ribosome is identical in informational content to the gene — but the gene itself never leaves the nucleus. [1 — links to complementary base pairing and faithful information transfer]

The strategy also lets different cell types tune their output to their job — bronchial epithelium needs CFTR ion-channel function to keep airway mucus hydrated, while skeletal muscle does not, and the dramatic difference in CFTR mRNA between these two tissues (100 vs 15) reflects exactly this. [1 — uses precise lesson terminology and ties biological purpose to the data]

Judgement: using a temporary mRNA copy is the more effective strategy across all four cell types shown. It allows one safely stored DNA copy to support many simultaneous and tissue-specific protein needs, preserves the integrity of the hereditary material, and — through complementary base pairing — still delivers a codon-faithful message to the ribosome. Ferrying DNA itself would satisfy none of these. [1 — justified judgement integrating data + reasoning]

Marking summary (out of 8): 1 — defines mRNA + identifies producer; 1 — uses ≥2 data points showing same-gene-different-mRNA; 1 — risk to DNA / single copy reason; 1 — damage/mutation reason; 1 — amplification reason with data link; 1 — base-pairing fidelity link; 1 — biological purpose connected to the data; 1 — justified judgement.