DNA & RNA Structure, Bonding, and Transcription – Comprehensive Notes

Molecular Building Blocks

• Nucleotide Composition (DNA & RNA)

  • 3 essential parts:
  • Phosphate group (-PO_4^{3-})
  • Pentose sugar
    • Deoxyribose ➔ DNA ("D" in DNA)
    • Ribose ➔ RNA ("R" in RNA)
    • Key chemical difference: ribose has an extra hydroxyl (–OH) on the 2' carbon; deoxyribose has only –H.
  • Nitrogenous base (heterocyclic ring)
  • Mnemonic: "P-S-B" → Phosphate–Sugar–Base forms every nucleotide.

• Nitrogenous Bases

  • DNA: Adenine (A), Thymine (T), Guanine (G), Cytosine (C).
  • RNA: Adenine (A), Uracil (U) replaces T, Guanine (G), Cytosine (C).
  • Structural families:
  • Purines: A & G (two-ring)
  • Pyrimidines: C, T, & U (single-ring)

Chemical Bonds & Forces

• Hydrogen Bonds (H-bonds)
  • Hold complementary bases together as "rungs" of the double helix.
  • Rule of thumb: H-bonding is strongest with \text{F, O, N} ("FON").
  • Pairing specifics:
  • \text{A} \;{\leftrightarrow}\; \text{T} (or U) via 2 H-bonds.
  • \text{G} \;{\leftrightarrow}\; \text{C} via 3 H-bonds (stronger).
• Phosphodiester Bonds
  • Covalently connect the 3'-OH of one nucleotide to the 5'-phosphate of the next ➔ forms the sugar-phosphate backbone of each strand.
  • Analogy: the zipper’s vertical rails.
• Van der Waals Forces
  • Weak stacking interactions between adjacent base pairs; contribute to helix stability.

DNA Double Helix Overview

• Two antiparallel strands (5' → 3' opposite 3' → 5').
• Zipper analogy:
  • Teeth = base pairs
  • Rails = sugar-phosphate backbone linked by phosphodiester bonds
  • Zipping = H-bond formation.

Strand Terminology

• Template (Non-coding) Strand: 3' → 5' DNA strand read by RNA polymerase.
• Coding (Non-template) Strand: 5' → 3' DNA strand; sequence mirrors mRNA except T ↔ U conversion.
• Complementary DNA Strand: generic term for the strand opposite any given sequence (obeys base-pair rules).

Central Dogma Focus: Transcription (DNA → RNA)

• Cellular Geography (Eukaryotes)

  • DNA confined to nucleus.
  • Ribosomes reside in cytoplasm (and on rough ER).
  • mRNA provides the necessary "messenger" conduit.

• Initiation

  • Enhancer sequences + transcriptional activator proteins begin assembly.
  • Promoter (incl. TATA box) = transcription start site.
  • General transcription factors + Mediator complex recruit RNA polymerase II (RNAP II).
  • DNA often loops so enhancers contact mediator/promoter region.

• Elongation

  • RNAP II moves along template 3' → 5'.
  • Adds ribonucleoside triphosphates (NTPs) to the mRNA 5' → 3'.
  • Reaction releases \text{PP}_i and is energetically favorable.
  • RNAP II possesses limited proofreading (base-pair correction) ability.

• Base-Pair Logic During Transcription

  • Template DNA A ⇒ mRNA U
  • Template DNA T ⇒ mRNA A
  • Template DNA G ⇒ mRNA C
  • Template DNA C ⇒ mRNA G

• Termination

  • Specific sequences or hairpins signal RNAP II release (not covered in depth in transcript).

Post-Transcriptional mRNA Processing (Eukaryotic)

1. 5' Cap Addition
   • 7-methyl-guanosine attached via 5'-5' triphosphate linkage.
   • Protects against exonucleases & aids nuclear export/ribosome binding.
2. 3' Poly-A Tail
   • ~250 adenine nucleotides added by poly-A-polymerase.
   • Enhances stability & translation efficiency.
3. Splicing
   • Introns (non-coding) removed; exons (coding) ligated.
   • Carried out by spliceosome (snRNP complex).
   • Result = mature (messenger) mRNA ready for export to cytoplasm.

Directionality Cheat-Sheet

• DNA template read: 3' → 5'
• RNA synthesized: 5' → 3'
• Finished mRNA presented to ribosome: 5' cap … coding region … 3' poly-A.

Classroom Examples & Analogies

• Zipper: visual for helix unzipping (helicase in replication; RNA polymerase in transcription).

• Jacket Teeth: each nucleotide “tooth” along one rail (strand) pairs with a complementary tooth across.

• F-O-N Mnemonic: remember atoms that form strong H-bonds with hydrogen.

• Practice Problem Walk-through Highlights

  • Given complementary strand ⇒ derive template by reversing base pair rules.
  • Given mRNA ⇒ derive template DNA (swap U for T, then pair).
  • Caveat: cannot derive complementary DNA directly from mRNA; must route through template first.

Enzyme & Organelle Connections

• RNA Polymerase II: main eukaryotic enzyme for mRNA synthesis; lowers activation energy for phosphodiester bond formation.
• Ribosomes: translate mRNA into polypeptide; located in cytoplasm or bound to rough ER.
• Endoplasmic Reticulum
  • Rough ER: studded with ribosomes, synthesizes proteins.
  • Smooth ER: synthesizes lipids.

Quick Reference Equations & Structures

• Generic phosphodiester linkage:
  \text{3'}\text{-OH (sugar)}\; + \; \text{5'}\text{-PO}4^{3-} \; \xrightarrow[\text{RNAP/DNAP}]{}\; \text{3'}\text{-O–PO}2\text{–O–5'}
• Number of H-bonds: \text{A–T} = 2 \quad ; \quad \text{G–C} = 3
• Poly-A tail length: \approx 250 \text{ A's}

Conceptual Connections

• Central Dogma: DNA (information storage) → mRNA (information carrier) → Protein (functional product).
• Mutations affecting splice sites, promoter/enhancer regions, or RNAP II can disrupt gene expression.
• Drugs targeting RNAP differences are antibacterial/antifungal strategies (ethical & therapeutic relevance).

Study Tips

• Drill base-pair rules until automatic.
• Practice labeling 5' & 3' ends; draw arrows for transcription direction.
• Work backward & forward between template, coding, and mRNA strands.
• Use the FON mnemonic for hydrogen bonding recognition.
• Visual aids (color-coded nucleotides, zipper diagrams) help cement the topology of DNA/RNA.