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DNA and Gene Transcription

Overview of DNA Coding Region

  • DNA consists of coding regions which are parts that can encode proteins.

  • Not all DNA in coding regions is used for protein synthesis.

Transcription Start Site (TSS)

  • TSS marks the beginning of transcription for a gene.

  • Important distinction: TSS is different from the start codon (AUG).

  • The start codon is located downstream of the TSS on the DNA strand.

Gene Structure in Eukaryotes

  • Eukaryotic genes consist of alternating exons and introns:

    • Exon: Coding sequences of DNA that are expressed.

    • Intron: Non-coding sequences of DNA that are spliced out.

  • Example structure: Exon 1, Intron 1, Exon 2, Intron 2, etc.

  • Exons and introns may be separated by thousands of bases.

Comparison with Prokaryotes (Bacteria)

  • In prokaryotes, genes are more compact. All necessary sequences for transcription are located adjacent to the coding sequences.

  • In eukaryotes, coding sequences (exons) and regulatory elements can be distanced from each other and may reside on different chromosomes.

Core Promoter

  • Core promoter is the DNA segment where RNA polymerase and transcription factors (TFs) bind to initiate transcription.

  • Core promoters are essential for transcription and must be located adjacent to the TSS.

  • Every gene requires a core promoter for the transcription process to initiate.

Transcription Factors (TFs)

  • TFs: Proteins involved in regulating the transcription of genes

    • General Transcription Factors: Required for the basic assembly of the transcription machinery (RNA polymerase). They bind to the core promoter.

    • Accessory Transcription Factors: Non-essential in general terms but can modify the rate of transcription.

  • Functionality of TFs:

    • Can increase or decrease the rate of transcription.

    • Regulate transcription by influencing RNA polymerase’s interaction with DNA and other proteins.

Regulation of Transcription

  • Interaction between different TFs and the core promoter impacts transcription regulation:

    • If factors are activated, more robust transcription occurs.

    • If factors are deactivated (e.g., TF II B), transcription cannot occur.

    • Importance of this regulation allows a cell to respond to different environments.

  • Eukaryotic signaling allows varied transcription rates based on environmental changes or cellular signals.

The Mediator Complex

  • The mediator is a complex of proteins that acts as a bridge between the transcription factors and RNA polymerase.

  • Mediator stabilizes the assembly of transcription machinery, enhancing transcription efficiency.

  • Its role involves:

    • Supporting the recruitment of general transcription factors.

    • Facilitating higher rates of transcription through stabilization of the complex.

Enhancers and Silencers

  • Enhancers: Sequences that, when bound by specific proteins (activators), increase transcription from a gene.

  • Silencers: Sequences that can bind repressor proteins to decrease or inhibit transcription.

  • Complexity of a gene's regulation may involve several enhancers and silencers.

    • Example: A gene can have multiple enhancers that activate it or silencers that inhibit it, depending on the cellular context.

Transcription Process Summary

  • Gene expression can vary based on:

    • The type and number of enhancers/silencers present.

    • Environmental stimuli or cellular signals induces different proteins affecting transcription.

  • Following transcription, the result is the synthesis of messenger RNA (mRNA).

  • At the 3' end of mRNA, a poly(A) tail (a long chain of adenine nucleotides) is added, a critical post-transcriptional modification.

mRNA Function in Neurons

  • mRNA is crucial for guiding neuronal development and connections.

  • In humans, approximately 20,000 genes may be expressed during development, influencing various cellular functions and behaviors from neuron to neuron.