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PHARMD GURU Page 1 INTRODUCTION: Gene expression is the process by which genetic information encoded in DNA is transcribed into RNA and translated into functional proteins. While the fundamental principles of gene expression are conserved across all life forms, prokaryotic and eukaryotic systems exhibit significant differences in their regulatory mechanisms and cellular processes. EXPRESSION SYSTEMS IN PROKARYOTES AND EUKARYOTES: A. COMPARISON OF PROKARYOTIC AND EUKARYOTIC GENE EXPRESSION: FEATURE PROKARYOTIC GENE EXPRESSION EUKARYOTIC GENE EXPRESSION Complexity Simple and efficient More complex with multiple regulatory layers Transcription and Translation Occur simultaneously (coupled process) Occur separately due to compartmentalization mRNA Structure Polycistronic (can encode multiple proteins in one mRNA) Monocistronic (each mRNA typically encodes one protein) RNA Processing Minimal processing; mRNA is directly translated Extensive processing (5' capping, splicing, polyadenylation) Regulatory Elements Operons regulate gene clusters Enhancers, silencers, and chromatin modifications provide fine control B. DIFFERENCES IN TRANSCRIPTION PROCESSES: 1. PROKARYOTIC TRANSCRIPTION:  RNA polymerase binds directly to the promoter with the help of sigma factors.  Produces mRNA that is ready for translation immediately.  Transcription and translation occur simultaneously in the cytoplasm. 2. EUKARYOTIC TRANSCRIPTION:  RNA polymerase II requires multiple transcription factors to initiate transcription. GENE EXPRESSION
PHARMD GURU Page 2  Involves various regulatory proteins that interact with enhancers and silencers.  Pre-mRNA undergoes modifications such as capping, splicing, and polyadenylation before being exported to the cytoplasm. C. DIFFERENCES IN TRANSLATION PROCESSES: 1. PROKARYOTIC TRANSLATION:  Begins while transcription is still ongoing due to the lack of compartmentalization.  Ribosomes bind to the Shine-Dalgarno sequence in mRNA to initiate translation. 2. EUKARYOTIC TRANSLATION: A. Translation occurs separately from transcription in the cytoplasm. B. The 5' cap structure is recognized by ribosomes, which scan the mRNA to find the start codon (AUG). C. More complex regulation through microRNAs and RNA-binding proteins. D. FUNCTIONAL IMPLICATIONS: 1. PROKARYOTIC SYSTEMS:  Rapid gene expression allows quick adaptation to environmental changes.  Operons enable coordinated regulation of multiple genes involved in the same pathway. 2. EUKARYOTIC SYSTEMS:  Provides sophisticated control over gene expression, supporting differentiation and development.  Introns enable alternative splicing, generating multiple protein isoforms from a single gene. GENETIC ELEMENTS THAT CONTROL GENE EXPRESSION: Gene expression is regulated by a variety of genetic elements that ensure proper transcriptional and translational control. These elements interact with proteins and signaling molecules to regulate gene activity based on developmental cues and
PHARMD GURU Page 3 environmental stimuli. A. KEY GENETIC ELEMENTS: 1. PROMOTERS:  Definition: DNA sequences located upstream of genes that serve as binding sites for RNA polymerase and transcription factors.  Types:  Core Promoter: Includes essential elements like the TATA box and initiator (Inr) sequence.  Proximal Promoter Elements: Located upstream of the core promoter, enhancing transcription factor binding.  Function: Determines the rate of transcription initiation and gene expression levels. 2. ENHANCERS:  Definition: DNA sequences that increase transcription rates by binding activator proteins.  Mechanism: Facilitates DNA looping, bringing transcription factors close to the promoter region.  Example: Immunoglobulin heavy chain enhancer is essential for high-level transcription in B cells. 3. SILENCERS:  Definition: DNA sequences that suppress gene expression by binding repressor proteins.  Function: Prevents unnecessary gene expression, ensuring tissue-specific gene regulation.  Example: NRSE/RE1 silencer represses neuronal genes in non-neuronal tissues. 4. INSULATORS:  Definition: Boundary elements that block interactions between enhancers and promoters of unintended genes.

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