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Chapter 3: Transcription & Translation

1. OVERVIEW

  1. Similar to DNA structure and synthesis, these subjects are closely related to Hematology/Oncology and Microbiology sections

  2. Thus, much of the focus is, as usual, on pharm and key disease applications (e.g., sickle cell anemia)

  3. In addition, 2 Biochemistry-specific topics that tend to show up on Step 1: Collagen synthesis and the lac operon

2. REGULATION OF GENE EXPRESSION

  1. There are several ways gene expression is regulated

    1. Initiation requires transcription factor binding to promoters (directly upstream of the gene)

      • Promoters are often cell-type specific

      • TATA and CAAT boxes are common features of promoters

    2. Expression is regulated by enhancers and silencers (anywhere around the gene)

    3. Methylation of DNA (CpG islands) mutes expression (see Chapter 2)

    4. Histone modification also regulates expression

      • Methylation of histones usually mutes expression

      • Acetylation of histones activates expression

  2. The lac operon is the example Step 1 likes to use to integrate these concepts

    1. Set of co-expressed genes used by bacteria to activate lactose metabolism when lactose is available and glucose is not

    2. Two regulatory steps must occur together to express the lac operon

      • Low glucose—activates CAP (binds enhancer)

      • High lactose—removes repressor protein (binds repressor)

  3. Mutations that disrupt gene regulation can be just as damaging as mutations in the gene's protein-coding region

    1. Protein deficiencies

      • In beta-thalassemia, mutations can occur in the promoter → less production of functional protein

      • Clinical: Anemia, hemolysis, weakness/fatigue

    2. Increased activity

      • Myc is a transcription factor that controls cell proliferation

      • Burkitt lymphoma, an aggressive form of cancer more common in children → caused by chromosomal translocation causing constitutive Myc expression

      • Clinical: Rapidly growing tumors on the jaw/face (endemic variant) or abdomen (sporadic); tumor lysis, hyperuricemia

Figure 3-1.

Regulation of gene expression.

An illustration shows the gene structure and regulation of gene expression through enhancers, silencers, and promoters. The lower strand has the 3' in the left and 5' in the right. The upper strand has the 5' in the left and 3' in the right. The leftmost portion of this structure has a horizontal region labeled enhancer. Another horizontal region is present slightly to the right of the enhancer and is labeled silencer. Slightly to the right of the silencer region is another narrow shaded region. On top of this is region is a bean-shaped structure labeled transcription factors. Another transcription factor is shown to its left and is moving toward the gene structure. Toward the center of the structure is a slightly wider horizontal region labeled promoter. This region has the C A T and T A T A boxes. An oblong structure labeled R N A polymerase is shown attached to the top of the strand at the promoter region between C A T and T A T A. To the right of the promoter region at a small distance is another wide horizontal region labeled the open reading frame. This region has another narrow rectangular region highlighted within it. The leftmost region of the strands has another narrow horizontal region that is not labeled. The caption reads, “regulation of gene expression.”
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Figure 3-2.

The lac operon.

An illustration shows the structure of the lac operon with the CA P site, promoter, operator, and lac genes regions represented horizontally from left to right.
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Figure 3-3.

Glucose and the lac operon.

Two illustrations show the activation effect of low glucose and the inhibition effect of high glucose on the lac operon. In the upper illustration, the low glucose leading to activation scenario is shown. Here, the enzyme adenylate cyclase is shown above the lac operon, which has the following regions present horizontally from left to right: C A P site, promoter, operator, and lac genes. The c A M P is shown to be attached to the adenylate cyclase. The C A P transcription factor is shown to be attached to the C A P site region of the lac operon. Another c A M P is shown attached to this C A P transcription factor. Right next to it is an oblong-shaped R N A polymerase, which is attached to the promoter region of the lac operon. A rightward arrow is shown to arise from the region between the operator and the lac genes. In the lower illustration, the high glucose leading to inhibition scenario is shown. Here the C A P transcription factor is shown above the CAP site of the lac operon, but away y fro lac operon. The R N A polymerase is also shown to be above and slightly away from the promoter and operator regions of the lac operon. In this scenario a cross mark is shown on top of the adenylate cyclase and many glucose molecules are shown to its right. The caption reads, “Glucose and the lac operon.”
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Figure 3-4.

Lactose and the lac operon.

Two illustrations show the inhibition effect of low lactose and the activation effect of high lactose on the lac operon. In the upper illustration, the low lactose leading to inhibition scenario is shown. Here, the lac operon is shown to have the following regions present horizontally from left to right: C A P site, promoter, operator, and lac genes. The C A P transcription factor is shown to be attached to the C A P site region of the lac operon. A lactose derivative or allolactose is shown attached to this C A P transcription factor. Right next to it is an oblong-shaped R N A polymerase, which is attached to the promoter region of the lac operon. A repressor protein is shown to be attached on top of the operator region of the lac operon. A rightward arrow is shown to arise from the region between the operator and the lac genes, but a cross mark is shown across it. In the lower illustration, the high lactose leading to activation scenario is shown. Here too the C A P transcription factor is shown on top of the CAP site of the lac operon. The R N A polymerase is shown to be attached to the promoter region of the lac operon. In this scenario a repressor protein is shown above the operator region of the lac operon but away from it. One lactose derivative or allolactose is shown to be present inside the repressor protein. In addition, many lactose derivatives are shown to the right of the repressor protein-lactose combination. The caption reads, “Lactose and the lac operon.”
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3. TRANSCRIPTION

  1. Four major types of RNA are found in the cell

    1. Ribosomal RNA (rRNA) is part of the ribosome, the main actor in translation

      • Synthesized by RNA polymerase I

    2. Messenger RNA (mRNA) encodes protein sequences

      • Synthesized by RNA polymerase II

      • Processed from heteronuclear RNA initially synthesized from DNA sequence in the nucleus

      • Amatoxins (poisonous mushrooms) inhibit RNA Pol II → apoptosis

    3. Transfer RNA (tRNA) links each mRNA codon into its corresponding amino acid

      • Synthesized by RNA polymerase III

    4. Micro RNA (miRNA) are short RNA sequences that do not encode protein

      • Regulates expression of proteins

      • Binds mRNA and prevents translation and/or tags for degradation

  2. RNA is processed to become mRNA

    1. Poly-adenylation tails and 7-methylguanosine triphosphate caps are added to stabilize each end of ...

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