Ch. 18 - Post-transcriptional Regulation in Eukaryotes

Klug - Concepts of Genetics 12th Edition

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Klug 12th Edition

Ch. 18 - Post-transcriptional Regulation in Eukaryotes

Problem 29

Chapter 18, Problem 29

RNAi is currently being tested as a therapeutic tool for genetic diseases and other conditions. Consider the following: cystic fibrosis caused by loss of function of the CFTR gene, HIV infection, and cancer caused by hyperactivity of a growth factor receptor. Which of these may be treatable by RNAi, and which not? Explain your reasoning.

Verified step by step guidance

Step 1: Understand the mechanism of RNA interference (RNAi). RNAi works by targeting and degrading specific messenger RNA (mRNA) molecules, thereby reducing or silencing the expression of particular genes. This means RNAi is effective in conditions where reducing or silencing a gene's expression can be beneficial.

Step 2: Analyze cystic fibrosis, which is caused by loss of function mutations in the CFTR gene. Since RNAi reduces gene expression, it would not be helpful here because the problem is insufficient or nonfunctional CFTR protein. RNAi cannot restore or increase gene function; it only decreases gene expression.

Step 3: Consider HIV infection. HIV relies on viral RNA and proteins to replicate. RNAi can be designed to target viral RNA sequences, potentially reducing viral replication. Therefore, RNAi may be a useful therapeutic tool against HIV by silencing viral genes.

Step 4: Examine cancer caused by hyperactivity of a growth factor receptor. In this case, the problem is excessive expression or activity of a gene. RNAi can target the mRNA of the overactive receptor, reducing its expression and potentially slowing cancer progression. Thus, RNAi may be effective here.

Step 5: Summarize the reasoning: RNAi is suitable for conditions caused by overexpression or presence of harmful RNA (like HIV or hyperactive receptors in cancer) but not for diseases caused by loss of gene function (like cystic fibrosis), where gene expression needs to be restored or enhanced rather than suppressed.

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Key Concepts

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

RNA Interference (RNAi) Mechanism

RNAi is a biological process where small RNA molecules inhibit gene expression by degrading target mRNA or blocking its translation. It is effective in silencing genes that are overexpressed or harmful, making it a potential therapeutic tool for conditions caused by gene overactivity.

Loss-of-Function vs. Gain-of-Function Mutations

Loss-of-function mutations result in reduced or absent protein activity, while gain-of-function mutations cause increased or new protein activity. RNAi can target and reduce harmful gene products in gain-of-function cases but cannot restore function lost due to gene inactivation.

Therapeutic Applications of RNAi in Genetic Diseases

RNAi is suitable for diseases where reducing harmful gene expression is beneficial, such as viral infections or cancers driven by overactive genes. However, it is ineffective for diseases like cystic fibrosis caused by gene loss, as RNAi cannot replace or restore missing gene function.

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