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Ch. 14 - Translation and Proteins
Klug - Concepts of Genetics  12th Edition
Klug12th EditionConcepts of Genetics ISBN: 9780135564776Not the one you use?Change textbook
Chapter 14, Problem 36a

The flow of genetic information from DNA to protein is mediated by messenger RNA. If you introduce short DNA strands (called antisense oligonucleotides) that are complementary to mRNAs, hydrogen bonding may occur and 'label' the DNA/RNA hybrid for ribonuclease-H degradation of the RNA. One study [Lloyd et al. (2001). Nucl. Acids Res. 29:3664–3673] compared the effect of different-length antisense oligonucleotides upon ribonuclease-H–mediated degradation of tumor necrosis factor (TNFα) mRNA. TNFα exhibits antitumor and pro-inflammatory activities. The following graph indicates the efficacy of various-sized antisense oligonucleotides in causing ribonuclease-H cleavage. Describe how antisense oligonucleotides interrupt the flow of genetic information in a cell.

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Antisense oligonucleotides are short, synthetic DNA strands designed to be complementary to specific messenger RNA (mRNA) sequences. This complementarity allows them to bind to the target mRNA through base pairing, forming a DNA/RNA hybrid.
The formation of the DNA/RNA hybrid is recognized by ribonuclease-H, an enzyme that specifically degrades the RNA strand in such hybrids. This degradation prevents the mRNA from being translated into a protein.
By targeting specific mRNAs, antisense oligonucleotides effectively interrupt the flow of genetic information from DNA to protein. This is because the mRNA, which serves as the template for protein synthesis, is destroyed before it can be translated by ribosomes.
The length of the antisense oligonucleotide can influence its binding efficiency and the subsequent degradation of the mRNA. Shorter or longer oligonucleotides may have varying levels of efficacy, as shown in the referenced study.
This mechanism can be used to selectively reduce the expression of specific proteins, such as tumor necrosis factor (TNFα), which plays a role in inflammation and tumor activity. By degrading TNFα mRNA, the production of this protein is inhibited, potentially altering cellular processes or disease outcomes.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Antisense Oligonucleotides

Antisense oligonucleotides are short, synthetic strands of DNA or RNA that are complementary to specific mRNA sequences. By binding to their target mRNA through base pairing, they can inhibit translation or promote degradation of the mRNA. This mechanism is crucial for regulating gene expression and can be utilized in therapeutic applications to silence genes associated with diseases.
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Ribonuclease H (RNase H)

Ribonuclease H is an enzyme that specifically degrades the RNA strand of RNA-DNA hybrids. When antisense oligonucleotides bind to their complementary mRNA, they form a hybrid that can be recognized by RNase H, leading to the degradation of the mRNA. This process effectively interrupts the flow of genetic information from DNA to protein by reducing the availability of mRNA for translation.
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Flow of Genetic Information

The flow of genetic information refers to the process by which genetic instructions are transferred from DNA to RNA and then to proteins, a concept often summarized as the central dogma of molecular biology. This flow is essential for cellular function and involves transcription (DNA to RNA) and translation (RNA to protein). Disrupting this flow, as with antisense oligonucleotides, can significantly impact protein synthesis and cellular activity.
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Related Practice
Textbook Question

How would the results vary in cross (a) of Problem 32 if genes A and B were linked with no crossing over between them? How would the results of cross (a) vary if genes A and B were linked and 20 map units (mu) apart?

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Textbook Question

Deep in a previously unexplored South American rain forest, a plant species was discovered with true-breeding varieties whose flowers were pink, rose, orange, or purple. A very astute plant geneticist made a single cross, carried to the F₂ generation, as shown:

P₁: purple × pink

F₁: all purple

F₂: 27/64 purple 16/64 pink 12/64 rose 9/64 orange

Based solely on these data, he proposed both a mode of inheritance for flower pigmentation and a biochemical pathway for the synthesis of these pigments. Carefully study the data. Create a hypothesis of your own to explain the mode of inheritance. Then propose a biochemical pathway consistent with your hypothesis. How could you test the hypothesis by making other crosses?

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Textbook Question

Many antibiotics are effective as drugs to fight off bacterial infections because they inhibit protein synthesis in bacterial cells. Using the information provided in the following table that highlights several antibiotics and their mode of action, discuss which phase of translation is inhibited: initiation, elongation, or termination. What other components of the translational machinery could be targeted to inhibit bacterial protein synthesis?

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Textbook Question

The flow of genetic information from DNA to protein is mediated by messenger RNA. If you introduce short DNA strands (called antisense oligonucleotides) that are complementary to mRNAs, hydrogen bonding may occur and 'label' the DNA/RNA hybrid for ribonuclease-H degradation of the RNA. One study [Lloyd et al. (2001). Nucl. Acids Res. 29:3664–3673] compared the effect of different-length antisense oligonucleotides upon ribonuclease-H–mediated degradation of tumor necrosis factor (TNFα) mRNA. TNFα exhibits antitumor and pro-inflammatory activities. The following graph indicates the efficacy of various-sized antisense oligonucleotides in causing ribonuclease-H cleavage. What general conclusion can be drawn from the graph?

539
views
Textbook Question

The flow of genetic information from DNA to protein is mediated by messenger RNA. If you introduce short DNA strands (called antisense oligonucleotides) that are complementary to mRNAs, hydrogen bonding may occur and 'label' the DNA/RNA hybrid for ribonuclease-H degradation of the RNA. One study [Lloyd et al. (2001). Nucl. Acids Res. 29:3664–3673] compared the effect of different-length antisense oligonucleotides upon ribonuclease-H–mediated degradation of tumor necrosis factor (TNFα) mRNA. TNFα exhibits antitumor and pro-inflammatory activities. The following graph indicates the efficacy of various-sized antisense oligonucleotides in causing ribonuclease-H cleavage. What factors other than oligonucleotide length are likely to influence antisense efficacy in vivo?

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Textbook Question

Infantile cardiomyopathy is a devastating disorder that is fatal during the first year of life due to defects in the function of heart muscles resulting from mitochondrial dysfunction. A study, performed by Götz et al. [(2011). Am. J. Hum. Genet. 88:635–642), identified two different causative mutations in the gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS). One mutation changes a leucine residue at amino acid position 155 to arginine (p.Leu155Arg). The other mutation changes arginine at position 592 to tryptophan (p.Arg592Trp). The mtAlaRS enzyme has an N-terminal domain (amino acids 36–481) that catalyzes tRNA aminoacylation and an internal editing domain (amino acids 484–782) that catalyzes deacylation in the case that the tRNA is charged with the wrong amino acid.

Consider the position of the disease causing missense mutations in the mtAlaRS gene in the context of the known protein domains of this enzyme. What predictions can you make about how these mutations impair protein synthesis within mitochondria in different ways?

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