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Overview of Transcription and Translation Decisions

• The processes of transcription and translation are critical in determining gene expression in cells.

• Once activated, these processes will proceed unless there is a regulatory decision to halt them.

• Today’s lecture focuses on the decision-makers that control when transcription and translation occur, emphasizing the role of various macromolecules involved.

Lecture Structure

• The lecture is divided into two parts:

  • Pre-Transcriptional Control: Involves decisions made before transcription begins.

  • Post-Transcriptional Control: Involves decisions after transcription occurs, particularly regarding the regulation of mRNA.

Pre-Transcriptional Control

Key Concepts

• Pre-transcriptional control directly involves DNA, as it determines when transcription will occur.

• Strategies:

  • Two methods for pre-transcriptional control

  • Subsequent strategies for post-transcriptional control will be discussed after.

Promoter and TATA Box

• The promoter is a key DNA sequence necessary for transcription initiation.

• The TATA box is a specific sequence within the promoter that is critical for forming the Transcription Initiation Complex (TIC).

Transcriptional Regulators (TRs)

• Regulatory Sequences:

  • Located within the promoter, these sequences are sites for TR binding and influence transcription activity.

• Types of TRs:

  • Enhancers: TRs that promote transcription (gas pedals).

  • Repressors: TRs that inhibit transcription (brake pedals).

  • TRs must possess:

    • A DNA Binding Domain to attach to regulatory sequences.

    • A Protein-Protein Interaction Domain to interact with the TIC.

DNA Interaction Looping

• TRs binding to regulatory sequences can influence events at the TIC through DNA looping, allowing distant interactions between elements.

• This creates a proximity effect even when the binding sites are upstream of the TIC.

Examples of Pre-Transcriptional Control

1. Transcriptional Regulators:

   • They affect transcription initiation through enhancing or repressing activity.

2. Chromatin Structure:

   • Chromatin consists of DNA wrapped around histones and can be remodeled through modifications (e.g., acetylation) to control transcription access.

   • Acetylation: Adding an acetyl group loosens DNA around histones, promoting transcription.

   • Deacetylation: Removing the acetyl group tightens DNA around histones, reducing transcription.

Post-Transcriptional Control

Overview

• Addressed decisions around mRNA after transcription, focusing on whether that mRNA will be translated into protein.

Examples of Post-Transcriptional Control

1. Translational Repressors:

   • Proteins that bind to the ribosomal binding site (RBS) on mRNA and physically block translation.

   • When no longer needed, these repressors can be removed allowing translation to commence.

2. Thermosensitive RNA:

   • Certain RNA structures change shape in response to temperature fluctuations, regulating translation based on environmental conditions.

   • For instance, bacteria can express virulence genes only at host body temperature, through structural changes in their mRNA.

3. MicroRNAs (miRNAs):

   • Small RNA molecules that bind to complementary sequences on mRNA, leading to translational repression or degradation.

   • Formed in the nucleus, they travel to target mRNAs carrying out repression through the RISC complex.

   • miRNAs can regulate multiple mRNAs, affecting protein synthesis and offering insights into diseases.

Importance of Regulation in Disease

• The regulation of transcription and translation is crucial for proper cellular function.

• Misregulation can lead to diseases such as cancer, Alzheimer's, and psychiatric disorders.

• Understanding these pathways is key in therapeutic advancements.

Conclusion

• Overall, the decision-making processes in transcription and translation involve complex interactions between various macromolecules, ensuring proper gene expression within the cell.