Unit 4: Gene Regulation
1. Concept of Constitutive, Regulated, Inducible, and Repressible Gene Expression
Gene regulation is the wide range of mechanisms used by cells to increase or decrease the production of specific gene products (protein or RNA).
A. Constitutive Gene Expression
These are genes that are expressed at a fixed rate, irrespective of the cell's environmental conditions. They are often referred to as "Housekeeping Genes" because they code for enzymes and proteins essential for basic cellular maintenance (e.g., enzymes for glycolysis).
B. Regulated Gene Expression
These genes are expressed only when their products are needed by the cell. This allows the cell to conserve energy and resources.
C. Inducible Gene Expression
An inducible gene is usually "off" but can be turned "on" by a specific molecule called an inducer. This typically happens in catabolic pathways where the gene is activated only when the substrate is present (e.g., the Lac operon).
D. Repressible Gene Expression
A repressible gene is usually "on" but can be turned "off" when a specific molecule, often the end product of the pathway (corepressor), reaches a certain concentration. This is common in anabolic (biosynthetic) pathways (e.g., the Trp operon).
2. Principles of Transcriptional Regulation: Lac Operon and Trp Operon
The Operon model, proposed by Jacob and Monod, is a unit of bacterial gene expression and regulation.
A. The Lac Operon (Inducible System)
The Lac operon is involved in the metabolism of lactose in E. coli. It consists of structural genes (lacZ, lacY, lacA) and regulatory elements.
- Structural Genes: lacZ (codes for beta-galactosidase), lacY (permease), and lacA (transacetylase).
- In the Absence of Lactose: The repressor protein binds to the operator, blocking RNA polymerase from transcribing the genes.
- In the Presence of Lactose: Allolactose (the inducer) binds to the repressor, changing its shape so it can no longer bind to the operator. RNA polymerase can then transcribe the genes.
B. The Trp Operon (Repressible System)
The Trp operon regulates the synthesis of the amino acid tryptophan. It is an example of negative repressible regulation.
- In the Absence of Tryptophan: The repressor is inactive and cannot bind to the operator. RNA polymerase transcribes the genes needed to synthesize tryptophan.
- In the Presence of Tryptophan: Tryptophan acts as a corepressor. It binds to the repressor, activating it. The active repressor-tryptophan complex binds to the operator, stopping transcription.
3. RNA Interference: miRNA and siRNA
RNA interference (RNAi) is a biological process in which RNA molecules inhibit gene expression or translation, by neutralizing targeted mRNA molecules.
A. siRNA (Small Interfering RNA)
- Derived from long double-stranded RNA (dsRNA) of viral or transposon origin.
- Dicer enzyme cuts dsRNA into short fragments (21-25 bp).
- They lead to highly specific cleavage of the target mRNA.
B. miRNA (microRNA)
- Encoded by the cell's own genome (endogenous).
- They usually lead to translational inhibition rather than direct cleavage because they often have imperfect complementarity to the target mRNA.
- Play a major role in regulating development and cellular processes.
4. Exam Focus Enhancements
Exam Tips
- Inducible vs Repressible: Remember: Lac is Lactose Inducible (LI); Trp is Tryptophan Repressible (TR).
- Operon Components: An operon = Promoter + Operator + Structural Genes. Regulatory genes (like lacI) are usually located nearby but are not technically part of the operon itself.
- RNAi difference: miRNA is Made by the cell (endogenous); siRNA is Stranger RNA (exogenous, like viruses).
Frequently Asked Questions
- Define the role of an inducer in the lac operon.
- What is meant by 'catabolite repression' in the context of the lac operon?
- Explain the mechanism of the RISC complex in RNA interference.
- Differentiate between the functions of siRNA and miRNA.
Common Mistakes
- Confusing Operator and Promoter. RNA polymerase binds to the Promoter; the repressor binds to the Operator.
- Assuming that lac genes are never expressed without lactose. There is always a low "basal" level of expression so the cell can sense lactose if it appears.