unit 5 central dogma

Central Dogma of Molecular Biology

Definition:

The central dogma refers to the fundamental process by which genetic information flows within a biological system. Specifically, it describes the sequential processes of transcription, in which DNA is transcribed into messenger RNA (mRNA), and translation, during which mRNA is translated into proteins. These proteins perform a variety of essential functions within the cells, influencing everything from metabolism to cellular structure and communication.

Key Steps:

DNA Holds the Genetic Code:

• Structure: DNA is a double-helical structure composed of nucleotides, which are the basic building blocks of DNA. Each nucleotide consists of a sugar, a phosphate group, and a nitrogenous base (adenine, thymine, cytosine, or guanine).

• Function: This genetic code is essential for the development, functioning, growth, and reproduction of all known living organisms, holding the instructions for building and maintaining the organism.

mRNA Transcription from DNA:

• Initiation: The process begins with the binding of RNA polymerase to a specific sequence in the DNA known as the promoter. This is a region of DNA that specifies where transcription begins.

• Process: During transcription, the DNA unwinds and the RNA polymerase traverses the DNA, synthesizing mRNA by adding complementary RNA nucleotides (where adenine pairs with uracil, instead of thymine). This creates a single strand of RNA that is complementary to the DNA template strand.

Protein Synthesis:

• Ribosomes: The mRNA is then transported to ribosomes, the cellular machinery responsible for protein synthesis. Ribosomes read the sequence of mRNA in groups of three nucleotide bases known as codons.

• Polypeptide Formation: Each codon corresponds to a specific amino acid, and through a series of steps involving transfer RNA (tRNA), amassing chains of amino acids forms polypeptides, which fold into functional proteins.

Organization of DNA:

Chromosomes:

• Structure: DNA is tightly coiled to form chromatin, with each DNA molecule wrapping around histones to create nucleosomes. This organization is critical during cell division (mitosis and meiosis) to ensure the accurate distribution of genetic material to daughter cells.

• Gene Accessibility: The packing state of DNA affects its transcription: tightly wound DNA is usually transcriptionally inactive, while loosely packed DNA (euchromatin) allows access for transcription machinery.

Template Strand Orientation:

• Directionality: The DNA template strand is read in the 3' to 5' direction, while mRNA is synthesized in the 5' to 3' direction. This orientation is critical for the correct assembly of the mRNA molecule, ensuring that when translated, the protein formed is in the correct sequence.

Transcription Process:

RNA Polymerase:

• Role: This enzyme plays a key role in synthesizing mRNA. It initiates transcription by unwinding the DNA and forming a complementary RNA strand.

Detailed Steps of Transcription:

1. Initiation: RNA polymerase binds to the promoter region of the gene and begins to separate the DNA strands.

2. Elongation: Complementary RNA nucleotides are added as RNA polymerase moves along the DNA, forming an RNA strand.

3. Termination: Transcription ends when RNA polymerase reaches a terminator sequence in the DNA, causing it to release the newly synthesized mRNA.

Role of Chromatin Structure in Gene Accessibility:

• Histones and Nucleosomes: The wrapping of DNA around histones forms nucleosomes, contributing to the compact structure of chromatin. This tight packing can inhibit transcription.

• Chemical Tags on Histones:

  • Methylation: The addition of methyl groups is typically associated with gene silence, preventing transcription.

  • Acetylation: Acetyl groups can be added to histones to loosen the DNA, promoting gene expression and transcription.

The Promoter and Transcription Factors:

Promoters:

• Definition: Promoters are sequences of DNA that indicate the start of a gene. They often include a TATA box, which serves as a binding site for transcription factors.

Transcription Factors:

• Function: These proteins bind to specific DNA sequences in the promoter region, playing an essential role in regulating the initiation of transcription. They can either activate or repress gene expression, affecting how much of a gene is expressed and when.

Enhancers:

• Regulatory Sequences: Enhancers are located distally from the promoter and can significantly increase transcription levels by facilitating interactions between DNA and transcription factors, potentially from far away on the DNA strand.

Messenger RNA Processing:

After transcription, pre-mRNA undergoes several processing steps:

1. Splicing: Introns (non-coding regions) are removed, and exons (coding regions) are spliced together by spliceosomes to produce a continuous coding sequence.

2. 5' Cap Addition: A modified guanine nucleotide is added to the 5' end of the mRNA for protection against degradation and to promote translation initiation.

3. Poly-A Tail Addition: A series of adenine nucleotides is added to the 3' end of mRNA, enhancing stability and facilitating export from the nucleus.

Translation Process:

Ribosome Function:

• Structure: Ribosomes consist of two major subunits (large and small) and contain three essential binding sites:

  • A site (Aminoacyl site): For incoming tRNA and its attached amino acid.

  • P site (Peptidyl site): Where the growing polypeptide chain is formed.

  • E site (Exit site): Where the discharged tRNA exits the ribosome after its amino acid has been added.

Translation Steps:

1. Initiation: The small ribosomal subunit binds to the mRNA and the first tRNA attaches to the start codon.

2. Elongation: The ribosome moves along the mRNA, and tRNA brings in amino acids corresponding to the codons. The ribosome facilitates the formation of peptide bonds between amino acids.

3. Termination: When a stop codon is reached, the ribosome disassembles, releasing the newly synthesized polypeptide chain.

Eukaryotic vs Prokaryotic Gene Expression:

Eukaryotes:

• Process: Gene transcription occurs in the nucleus; pre-mRNA is processed to mature mRNA before it exits to ribosomes in the cytoplasm for translation. Eukaryotic cells can form polyribosomes, enhancing translation efficiency by allowing multiple ribosomes to translate a single mRNA simultaneously.

Prokaryotes:

• Concurrent Transcription and Translation: Lacking a defined nucleus, prokaryotes can simultaneously perform transcription and translation in the cytoplasm, allowing for rapid and efficient protein synthesis in response to environmental changes.

Study Tips:

To enhance understanding of the central dogma and molecular biology concepts, consider the following strategies:

• Collaborative Learning: Engage in study groups to explain complex concepts to peers, reinforcing understanding and retention.

• Utilize Resources: Leverage handouts, diagrams, and visual aids that clarify processes, providing a better context for mechanisms discussed during lectures and exercises.

• Active Participation: Take part in discussions and ask questions in class to deepen comprehension and encourage critical thinking about molecular biology concepts.