Biochemistry BUCM Gene Expression Quiz

Study Notes

Gene Expression

Multistep process leading to functional gene products: RNA or protein.
Cells regulate production of RNA and protein from DNA.

Central Dogma of Molecular Biology

Two main gene groups:
- Structural Genes: Protein coding genes comprising ~20,400 in humans, making up ~2% of human DNA.
- Regulatory Genes: Genes that regulate structural protein production, accounting for ~98% of human DNA.

Regulation of Prokaryotic Gene Expression

Operons are clusters of genes transcribed together as a single mRNA molecule.
Lactose Operon: Contains an operator that binds a repressor protein, blocking mRNA production unless an inducer is present.
- lacZ gene: Codes for β-galactosidase, hydrolyzing lactose to glucose and galactose.
- lacY gene: Codes for permease, facilitating lactose entry into cells.
- lacA gene: Codes for thiogalactosidetransacetylase, acetylating lactose.
Trp Operon regulation involves:
- Trp Repressor: Active when tryptophan is present, blocking transcription.
- Attenuation: Reduces expression when tryptophan levels are high by preventing full transcription completion.
- Ribosome behavior during translation influences hairpin structure formation in mRNA, affecting termination of transcription.

Attenuation Mechanism

Leader region: Contains attenuator, which can form hairpins influencing transcription.
Low tryptophan: Ribosome stalls, preventing formation of terminator hairpin; transcription continues.
High tryptophan: Ribosome quickly translates leader, forming terminator hairpin that leads to transcription termination.

Regulation of Eukaryotic Gene Expression

Eukaryotic gene expression is complex, regulated mainly during transcription.
Gene components:
- Exons: Expressed DNA sequences coding for proteins.
- Introns: Non-expressed sequences between exons.
- Start site: RNA Polymerase II binding location.
- Promoters: Core promoters (e.g., TATA box) present in all eukaryotic genes; upstream promoters vary per gene.
- Enhancers/Silencers: DNA sequences that modulate transcription rates from a distance.

Transcription Factors

Proteins that regulate transcription by binding to DNA sequences.
Structure:
- DNA Binding Domain (DBD): Binds specific DNA sequences.
- Transactivation Domain (TAD): Binds co-regulatory proteins.
- Signal-Sensing Domain (SSD): Occasionally present, allows interaction with signaling molecules.

Clinical Correlates

Huntington’s Disease (HD):
- Autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the HTT gene.
- Leads to mutant huntingtin protein accumulation in neurons, causing cell death and symptoms including motor dysfunction and cognitive decline.
- Ongoing research focuses on gene silencing therapies.
Duchenne Muscular Dystrophy (DMD):
- X-linked recessive disorder marked by progressive muscle degeneration due to mutations in the DMD gene encoding dystrophin.
- Characterized by muscle fiber integrity loss, delayed motor milestones, and potential cardiopulmonary complications.
- Therapies like exon skipping aim to restore functional dystrophin production.

Muscle Stabilization in DMD

Copolymer-based strategies enhance muscle membrane stability by preventing extracellular calcium influx, promoting muscle health despite dystrophin absence.

Description

This quiz focuses on gene expression, a crucial multistep process leading to the production of RNA or protein in cells. It explores the regulation of gene products and the principles underlying the central dogma of molecular biology. Suitable for students following the BUCM biochemistry course for 2024-2025.