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C-terminal domain (CTD)

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Biochemistry

Definition

The C-terminal domain (CTD) is a crucial part of the RNA polymerase II enzyme that plays a significant role in eukaryotic transcription. It consists of multiple repeats of a heptapeptide sequence, typically YSPTSPS, and is essential for the recruitment of various factors involved in RNA processing and transcriptional regulation. The CTD undergoes phosphorylation, which is key to coordinating the different stages of transcription and influencing mRNA processing events.

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5 Must Know Facts For Your Next Test

  1. The CTD consists of repeated heptapeptide sequences that are critical for the regulation of transcriptional elongation and mRNA processing.
  2. Phosphorylation of the serine residues within the CTD is an important regulatory mechanism that helps transition RNA polymerase II from initiation to elongation phases of transcription.
  3. Different kinases phosphorylate specific serine residues at different stages, allowing for a complex interplay between transcription and mRNA processing events.
  4. The CTD interacts with various RNA processing factors, including those involved in capping, splicing, and polyadenylation, ensuring efficient maturation of mRNA.
  5. Mutations in the CTD can lead to defects in transcription regulation and mRNA processing, impacting gene expression and cell function.

Review Questions

  • How does the structure of the C-terminal domain (CTD) contribute to its function in eukaryotic transcription?
    • The CTD is composed of multiple repeats of a heptapeptide sequence that provide binding sites for various transcription factors and processing enzymes. This modular structure allows it to interact dynamically with different proteins during transcription, facilitating the recruitment of necessary factors for both transcriptional elongation and subsequent mRNA processing steps. The repetitive nature of the CTD means that it can undergo various post-translational modifications like phosphorylation, which further enhances its versatility in regulating gene expression.
  • Discuss the role of phosphorylation in the function of the C-terminal domain (CTD) during transcription.
    • Phosphorylation plays a critical role in modulating the activity of the CTD throughout different phases of transcription. Specific kinases phosphorylate serine residues on the CTD to signal transitions from initiation to elongation. For instance, hyperphosphorylation is typically associated with active elongation, while dephosphorylation can signal termination or recycling. This phosphorylation state effectively coordinates transcriptional machinery and ensures proper coupling between transcription and mRNA processing.
  • Evaluate how mutations in the C-terminal domain (CTD) could affect gene expression and cellular processes.
    • Mutations in the CTD can disrupt its normal function by altering its phosphorylation patterns or binding interactions with necessary cofactors. Such disruptions can lead to improper regulation of transcriptional elongation or inefficient mRNA processing, resulting in altered gene expression profiles. This can have downstream effects on cellular processes such as growth, differentiation, and response to environmental signals. Ultimately, these mutations can contribute to diseases like cancer, where gene regulation becomes critically deregulated.

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