Table C contains DNA-sequence information compiled by Marilyn Kozak (1987). The data consist of the percentage of A, C, G, and T at each position among the 12 nucleotides preceding the start codon in 699 genes from various vertebrate species and at the first nucleotide after the start codon. (The start codon occupies positions +1 to +3 and the first nucleotide immediately after the start codon occupies position +4) Use the data to determine the consensus sequence for the 13 nucleotides ( -12 to -1 and +4) surrounding the start codon in vertebrate genes.
Table of contents
- 1. Introduction to Genetics51m
- 2. Mendel's Laws of Inheritance3h 37m
- 3. Extensions to Mendelian Inheritance2h 41m
- 4. Genetic Mapping and Linkage2h 28m
- 5. Genetics of Bacteria and Viruses1h 21m
- 6. Chromosomal Variation1h 48m
- 7. DNA and Chromosome Structure56m
- 8. DNA Replication1h 10m
- 9. Mitosis and Meiosis1h 34m
- 10. Transcription1h 0m
- 11. Translation58m
- 12. Gene Regulation in Prokaryotes1h 19m
- 13. Gene Regulation in Eukaryotes44m
- 14. Genetic Control of Development44m
- 15. Genomes and Genomics1h 50m
- 16. Transposable Elements47m
- 17. Mutation, Repair, and Recombination1h 6m
- 18. Molecular Genetic Tools19m
- 19. Cancer Genetics29m
- 20. Quantitative Genetics1h 26m
- 21. Population Genetics50m
- 22. Evolutionary Genetics29m
11. Translation
Translation
Problem 36a
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. Describe how antisense oligonucleotides interrupt the flow of genetic information in a cell.

1
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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