Gene Expression Regulation

Gene Expression Regulation

• Gene expression is the process of using genetic information to synthesize functional gene products (RNAs and proteins).
• Regulation of gene expression allows cells to control which genes are expressed, and to what extent, in response to changing conditions.
• Housekeeping genes (constitutive genes) are expressed constantly, providing essential cellular functions.
• Regulated genes respond to internal and external signals, adapting to specific environmental or developmental needs.
• Gene expression can be controlled at multiple levels:
  • Transcriptional regulation: Controlling the initiation and rate of transcription.
  • Post-transcriptional regulation: Modifying mRNA transcripts after transcription.
  • Translational regulation: Affecting the initiation and rate of protein synthesis.
  • Post-translational regulation: Modifying proteins after translation.

Cis- and Trans-Acting Regulatory Elements

• Cis-acting elements are DNA sequences that regulate the expression of genes on the same DNA molecule. They include:
  • Promoters: DNA sequences that bind RNA polymerase, initiating transcription.
  • Enhancers: DNA sequences that enhance transcription, often located far from the gene they regulate.
  • Silencers: DNA sequences that repress transcription.
• Trans-acting elements are proteins or RNA molecules that bind to cis-acting elements to regulate gene expression. They include:
  • Transcription factors: Proteins that bind to promoter, enhancer, and silencer sequences to control the rate of transcription.
  • RNA-binding proteins: Proteins that bind to mRNA molecules, influencing their stability, processing, and translation.

Gene Regulation in Prokaryotes

• Prokaryotes regulate gene expression to conserve energy, adapt rapidly to environmental changes, and optimize metabolic efficiency.
• Operons: Groups of functionally related genes transcribed as a single mRNA unit, allowing for coordinated regulation.
• Repressible Operons (anabolic): Operons that are active by default and are repressed by the accumulation of the product of the pathway they encode.
  • trp operon: Synthesizes tryptophan, and is repressed by high tryptophan levels.
• Inducible Operons (catabolic): Operons that are inactive by default and are induced by the presence of the substrate they metabolize.
  • lac operon: Breaks down lactose, and is induced by the presence of lactose.
• Transcription Elongation Control - Attenuation: A mechanism that fine-tunes the expression of genes involved in amino acid biosynthesis, using ribosome stalling at Trp codons to regulate transcription elongation.
• Riboswitches: RNA regulatory elements in 5' untranslated regions of mRNA that bind specific metabolites, influencing gene expression.

Gene Regulation in Eukaryotes

• Eukaryotes regulate gene expression to enable cell differentiation, development, homeostasis, and responses to environmental cues.
• Chromatin structure influences gene expression by affecting the accessibility of DNA to transcription machinery.
• Histone modifications: Chemical modifications of histone proteins that alter chromatin structure, influencing gene expression. Acetylation generally activates genes, while methylation can repress them.
• DNA methylation: The addition of a methyl group to cytosine within DNA sequences, often leading to repression of gene expression. Methylated CpG sequences can attract methyl-binding proteins (MBDs) and histone deacetylases (HDACs), leading to gene silencing.
• Genomic imprinting: The differential expression of maternal and paternal alleles of certain genes, often achieved by specific methylation patterns.

Post-Transcriptional Regulation

• RNA processing: Regulation of mRNA transcripts after transcription, influencing their stability and translation efficiency through:
  • Splicing: Removal of introns from pre-mRNA molecules.
  • Capping: The addition of a 5' cap to mRNA molecules.
  • Polyadenylation: The addition of a poly(A) tail to mRNA molecules.

Control by Non-coding RNA

• MicroRNAs (miRNAs): Small, non-coding RNA molecules that regulate gene expression by binding to complementary sites on target mRNAs, leading to mRNA degradation or translation inhibition.
• Small interfering RNAs (siRNAs): Similar to miRNAs but are often derived from double-stranded RNA molecules. siRNAs can silence gene expression by targeting specific mRNAs for degradation.
• Long non-coding RNAs (lncRNAs): Long, non-coding RNA molecules that have diverse roles in gene expression regulation. Some lncRNAs act as scaffolds, bringing together regulatory proteins at specific genomic loci, while others can interact with DNA or mRNA.

This quiz explores the intricate mechanisms of gene expression regulation, highlighting the difference between housekeeping and regulated genes. It covers various levels of control, including transcriptional, post-transcriptional, translational, and post-translational regulation, essential for cellular adaptation to environmental changes.