7.6 Gene Expression

5 min read•august 22, 2024

Gene expression is the process of turning DNA into functional products like proteins. It's crucial for cells to develop specialized functions and for organisms to grow properly. When gene expression goes wrong, it can lead to diseases like cancer.

Prokaryotes and eukaryotes regulate genes differently. Prokaryotes use operons to control groups of genes, while eukaryotes have more complex systems. Eukaryotes can control gene expression at multiple levels, from DNA accessibility to protein modifications.

Gene expression and cellular function

The central dogma and flow of genetic information

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  • Gene expression is the process by which the genetic information encoded in DNA is used to direct the synthesis of functional gene products, primarily proteins, which determine the phenotype of the cell and the organism
  • The central dogma of molecular biology describes the flow of genetic information from DNA to RNA to proteins
    • DNA serves as the template for RNA synthesis (transcription)
    • RNA serves as the template for protein synthesis (translation)

Importance of gene expression in development and disease

  • Gene expression is essential for cellular differentiation
    • Allows cells with identical genomes to develop into specialized cell types with distinct functions (neurons, muscle cells, epithelial cells)
  • Proper regulation of gene expression is crucial for normal development
    • Ensures that the right genes are expressed at the right time, in the right place, and in the appropriate amount
  • Dysregulation of gene expression can lead to various diseases
    • Developmental disorders
    • Metabolic disorders
    • Cancer

Prokaryotic vs Eukaryotic gene regulation

Prokaryotic gene regulation through operons

  • In prokaryotes, gene expression is primarily regulated at the transcriptional level through the use of operons
    • Operons are clusters of genes under the control of a single promoter and regulated by transcription factors that respond to environmental signals
  • The lac operon in E. coli is a well-studied example of negative regulation
    • The presence of glucose represses the expression of genes involved in lactose metabolism
    • The absence of glucose and presence of lactose induces their expression
  • The trp operon is an example of negative repression
    • The presence of tryptophan represses the expression of genes involved in tryptophan biosynthesis
    • The absence of tryptophan induces their expression

Multilevel regulation of gene expression in eukaryotes

  • In eukaryotes, gene expression is regulated at multiple levels
    • Transcriptional
    • Post-transcriptional
    • Translational
    • Post-translational
  • Transcriptional regulation in eukaryotes involves the interaction of transcription factors with cis-regulatory elements (promoters, enhancers) to control the initiation and rate of transcription
  • Chromatin structure and epigenetic modifications play a significant role in regulating gene expression by altering the accessibility of DNA to transcription factors
    • DNA methylation
    • Histone modifications
  • Post-transcriptional regulation in eukaryotes includes mechanisms that modify the stability, localization, and translation of mRNA
    • Alternative splicing
    • RNA editing
    • MicroRNA-mediated gene silencing
  • Translational and post-translational regulation in eukaryotes involve mechanisms that control the rate of protein synthesis and the activity of the resulting proteins
    • Ribosome recruitment
    • Protein folding
    • Post-translational modifications

Transcription factors in gene regulation

Structure and function of transcription factors

  • Transcription factors are proteins that bind to specific DNA sequences, called cis-regulatory elements, in the promoter or enhancer regions of genes to regulate their expression
  • Transcription factors can act as activators or repressors
    • Activators enhance the recruitment of RNA polymerase and increase the rate of transcription
    • Repressors inhibit the recruitment of RNA polymerase and decrease the rate of transcription
  • The binding of transcription factors to DNA is mediated by specific DNA-binding domains
    • Zinc fingers
    • Helix-turn-helix motifs
    • Leucine zippers

Transcription factor networks and regulation

  • Transcription factors often work in combination, forming complex regulatory networks
    • Integrate multiple signals to fine-tune gene expression in response to various environmental and developmental cues
  • The activity of transcription factors can be modulated by various mechanisms
    • Post-translational modifications (phosphorylation, acetylation)
    • Protein-protein interactions
    • Subcellular localization
  • Mutations in transcription factors or their binding sites can lead to altered gene expression and various genetic disorders
    • Developmental abnormalities
    • Cancer

Post-transcriptional and translational control

Alternative splicing and RNA editing

  • Alternative splicing is a post-transcriptional mechanism that allows a single gene to produce multiple mRNA isoforms
    • Leads to the synthesis of different protein variants with distinct functions
    • Selection of alternative splice sites is regulated by cis-acting regulatory sequences and trans-acting splicing factors
    • Plays a crucial role in generating protein diversity, particularly in complex organisms (humans)
  • RNA editing is another post-transcriptional mechanism that modifies the nucleotide sequence of the mRNA
    • Can alter the amino acid sequence of the encoded protein or introduce premature stop codons
    • Most common form in mammals is adenosine-to-inosine (A-to-I) editing, catalyzed by the ADAR family of enzymes
    • Can modulate protein function, alter mRNA stability, and regulate gene expression
    • Dysregulation has been implicated in various neurological disorders and cancers

MicroRNAs and translational control mechanisms

  • MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression post-transcriptionally
    • Base-pair with complementary sequences in the 3' untranslated regions (UTRs) of target mRNAs
    • Binding can lead to mRNA degradation or translational repression, depending on the degree of complementarity
    • Play essential roles in various biological processes (development, differentiation, disease)
    • Expression is often tissue-specific and developmentally regulated
  • Translational control mechanisms regulate the rate and efficiency of protein synthesis, allowing rapid changes in protein levels
    • Ribosome recruitment and initiation of translation can be regulated by the interaction of translation initiation factors with specific sequences in the 5' UTR of the mRNA (5' cap, internal ribosome entry sites)
    • Elongation and termination steps of translation can be modulated by the availability of charged tRNAs, the presence of rare codons, and the action of regulatory proteins
  • Post-translational modifications (PTMs) are covalent modifications of proteins that occur after their synthesis
    • Examples include phosphorylation, glycosylation, and ubiquitination
    • Can alter protein function, stability, and localization
    • Catalyzed by specific enzymes and are reversible, allowing dynamic regulation of protein activity
    • Play crucial roles in various cellular processes (signal transduction, cell cycle regulation, protein degradation)
    • Dysregulation is associated with numerous diseases (cancer, neurodegenerative disorders)
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