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Transcription & RNA Processing | Steps, Enzymes & Clinical Correlations | MBBS Biochemistry | USMLE Step 1

👋 Hey future doctors and biochem learners! The central dogma of molecular biology states: DNA → RNA → Protein. The first step, Transcription, is how genetic information in DNA is copied into RNA. But before RNA can function, it undergoes processing modifications.

This lecture breaks down Transcription and RNA Processing step-by-step, with clinical correlations that are favorites in MBBS, NEET PG, FMGE, and USMLE Step 1 exams. 🧬📚

🌟 Transcription

Definition: Synthesis of RNA from DNA using RNA polymerase.

Direction: DNA template read 3’ → 5’, RNA synthesized 5’ → 3’.

Key Enzymes:

Prokaryotes: 1 RNA polymerase (sigma factor for initiation).

Eukaryotes:
• RNA Pol I → rRNA (except 5S).
• RNA Pol II → mRNA (protein coding), snRNA.
• RNA Pol III → tRNA, 5S rRNA.

Steps:
1️⃣ Initiation: RNA polymerase binds promoter (TATA box, CAAT box).
2️⃣ Elongation: RNA chain grows, complementary to DNA template.
3️⃣ Termination: Hairpin loop (prokaryotes) or specific termination signals.

🌟 RNA Processing (in Eukaryotes)

Occurs mainly in the nucleus before mRNA becomes functional:

1️⃣ Capping (5’ end):

Addition of 7-methylguanosine cap.

Protects mRNA from degradation, helps ribosome binding.

2️⃣ Polyadenylation (3’ end):

Poly-A tail (~200 A’s) added by Poly-A polymerase.

Increases stability, regulates transport to cytoplasm.

3️⃣ Splicing:

Removal of introns, joining of exons by spliceosome (snRNPs).

Conserved sequences at intron-exon junctions.

Clinical 🩺: Defects → diseases like β-thalassemia (abnormal splicing).

🌟 Other RNAs

tRNA processing: addition of CCA tail (for amino acid attachment).

rRNA processing: cleavage, modification, assembly into ribosomal subunits.

🩺 Clinical Correlations

α-Amanitin (mushroom toxin): inhibits RNA Pol II → severe hepatotoxicity.

Rifampin: inhibits prokaryotic RNA polymerase → TB therapy.

Actinomycin D: inhibits RNA synthesis in both prokaryotes & eukaryotes.

Splicing errors: β-thalassemia, lupus (anti-snRNP antibodies).

🎯 Exam Integration

RNA Pol II → mRNA.

5’ Cap, 3’ Poly-A tail, Splicing = key eukaryotic modifications.

Drugs & toxins target transcription (Rifampin, α-amanitin, Actinomycin D).
👉 A favorite area for both recall and clinical vignette questions in USMLE Step 1 & NEET PG.

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