18.1 Molecular Properties of Genes & the Central Dogma
Key Takeaways
- The central dogma is the directional flow DNA → RNA → protein; transcription copies DNA into RNA and translation decodes RNA into polypeptide on ribosomes (PA-CAT Bulletin of Information, rev. 20240815, Table 8).
- Elongation is the transcription stage in which RNA polymerase builds an RNA chain complementary to the DNA template, reading 3'→5' and synthesizing RNA 5'→3' without a primer — the Bulletin sample item tests this directly.
- A eukaryotic gene includes a promoter, enhancers/silencers, exons, introns, a 5' UTR and a 3' UTR; pre-mRNA is processed by 5' capping, spliceosome-mediated splicing, and 3' polyadenylation before export.
- The genetic code is triplet, degenerate, non-overlapping, and nearly universal; AUG is the start codon (Met) and UAA/UAG/UGA are stop codons.
- RNA polymerase lacks 3'→5' proofreading, so transcription error rates (~1 in 10^4–10^5) exceed DNA replication errors.
The Central Dogma of Molecular Biology
The central dogma describes the directional flow of genetic information: DNA → RNA → protein. In the PA-CAT genetics block (Bulletin of Information, rev. 20240815, Table 8 — Molecular Properties of Genes), this framework underlies roughly a third of the 26 genetics items. Transcription copies a gene's DNA sequence into RNA; translation decodes that RNA into a polypeptide. Replication (DNA → DNA) and reverse transcription (RNA → DNA, in retroviruses) are related processes, but the canonical path tested is DNA → RNA → protein.
Gene Structure: Exons, Introns, UTRs, Promoters, Enhancers
A eukaryotic gene is more than its coding sequence. Key landmarks:
| Element | Location | Function |
|---|---|---|
| Promoter | Immediately 5' of the transcription start site | Binds RNA polymerase II and general transcription factors (e.g., TATA box) |
| Enhancer | Upstream, downstream, or intronic — can be far away | Binds activators; loops to promoter to boost transcription |
| Exons | Within the transcribed region | Sequences retained in mature mRNA; mostly code for protein |
| Introns | Between exons | Non-coding intervening sequences; removed by splicing |
| 5' UTR | Start of mature mRNA, before start codon | Ribosome binding and translational regulation |
| 3' UTR | After stop codon, before poly-A tail | Stability, localization, miRNA binding |
| Silencer | Various positions | Binds repressors to decrease transcription |
Prokaryotic genes generally lack introns and are often organized into operons (covered in §18.4). The distinction between the template strand (the one RNA polymerase reads, 3'→5') and the coding strand (identical in sequence to the RNA, except T for U) is a common exam point.
Transcription: Initiation, Elongation, Termination
Transcription has three stages. In initiation, RNA polymerase (RNA pol) binds the promoter with general transcription factors (TFIID, TFIIH, and others), forming the pre-initiation complex. In elongation, RNA polymerase builds an RNA chain complementary to the DNA template strand, reading the template 3'→5' and synthesizing RNA 5'→3'. This is the stage the PA-CAT Bulletin sample item targets: the question asks which stage of transcription involves RNA polymerase building an RNA chain — the answer is elongation. RNA polymerase does not require a primer (unlike DNA polymerase) and lacks 3'→5' proofreading exonuclease activity, so transcription error rates are higher (~1 in 10^4–10^5) than DNA replication errors. In termination, eukaryotes use a polyadenylation signal (AAUAAA) followed by cleavage and polymerase release; prokaryotes use Rho-dependent or Rho-independent (intrinsic hairpin) terminators.
| Stage | Prokaryotes | Eukaryotes |
|---|---|---|
| Initiation | σ-factor + core polymerase | RNA pol II + general transcription factors |
| Elongation | Single RNA polymerase | RNA pol II (must traverse nucleosomes) |
| Termination | Rho-dependent or hairpin terminator | AAUAAA signal + endonucleolytic cleavage |
RNA Processing (Eukaryotes Only)
Pre-mRNA is modified in three ways before nuclear export:
- 5' capping — a 7-methylguanosine cap is added co-transcriptionally; it protects the transcript from 5' exonucleases and serves as the ribosome's binding signal for translation initiation.
- Splicing — the spliceosome (small nuclear ribonucleoproteins snRNPs U1–U6) removes introns and ligates exons at conserved GU...AG splice sites. Alternative splicing multiplies protein isoforms from one gene.
- 3' polyadenylation — after cleavage at the AAUAAA signal, a ~150–250 adenosine poly-A tail is added; it aids nuclear export, stability, and translation efficiency.
Translation: Ribosome, tRNA, Codons
Translation occurs in the cytoplasm on ribosomes (80S in eukaryotes: 60S + 40S subunits; 70S in prokaryotes: 50S + 30S). Transfer RNA (tRNA) is the adaptor molecule: each tRNA is charged with a specific amino acid by an aminoacyl-tRNA synthetase and bears an anticodon that base-pairs with a complementary codon on mRNA.
The genetic code has these properties:
- Triplet — three nucleotides encode one amino acid.
- Degenerate — multiple codons specify the same amino acid (61 sense codons → 20 amino acids).
- Non-overlapping and read from a fixed start codon.
- Nearly universal — the same codons specify the same amino acids in nearly all organisms (mitochondrial and a few nuclear codes have minor deviations).
- AUG is the start codon (methionine); UAA, UAG, UGA are stop (nonsense) codons.
Translation proceeds in three stages. Initiation: the small ribosomal subunit + mRNA + initiator tRNA (Met) assemble, then the large subunit joins. Elongation: aminoacyl-tRNA enters the A site, the peptidyl transferase activity of the large subunit's rRNA (a ribozyme) forms the peptide bond, and the ribosome translocates, moving the growing chain to the P site and the deacylated tRNA to the E site. Termination: release factors recognize the stop codon and the polypeptide is released.
Regulation Preview
Gene expression is regulated at multiple levels — chromatin accessibility, transcription initiation, RNA processing (alternative splicing, poly-A site choice), mRNA stability and export, translation, and post-translational modification. Section 18.4 covers prokaryotic operons and eukaryotic epigenetic regulation in depth.
Which stage of transcription is described by RNA polymerase synthesizing an RNA chain complementary to the DNA template strand?
Which RNA processing event removes introns from pre-mRNA?