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Ch. 17+18 - Transcriptional Regulation in Eukaryotes
Chapter 17, Problem 25

Incorrectly spliced RNAs often lead to human pathologies. Scientists have examined cancer cells for splice-specific changes and found that many of the changes disrupt tumor-suppressor gene function [Xu and Lee (2003). Nucl. Acids Res. 31:5635–5643]. In general, what would be the effects of splicing changes on these RNAs and the function of tumor-suppressor gene function? How might loss of splicing specificity be associated with cancer?

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span>Understand the role of splicing in RNA processing: Splicing is a crucial step in the processing of pre-mRNA, where introns are removed, and exons are joined to form mature mRNA. This process is essential for the correct translation of genetic information into proteins.</span
span>Recognize the function of tumor-suppressor genes: Tumor-suppressor genes are responsible for regulating cell growth and division. They help prevent uncontrolled cell proliferation, which can lead to cancer.</span
span>Identify the impact of incorrect splicing on mRNA: Incorrect splicing can lead to the inclusion of introns or the exclusion of exons in the mRNA. This can result in the production of non-functional or harmful proteins, or even the complete absence of a protein.</span
span>Connect splicing errors to tumor-suppressor gene dysfunction: If splicing errors occur in tumor-suppressor genes, the resulting mRNA may not produce functional tumor-suppressor proteins. This loss of function can remove critical checks on cell division, contributing to cancer development.</span
span>Consider the broader implications of splicing specificity loss: Loss of splicing specificity can lead to widespread changes in gene expression, affecting multiple pathways and potentially leading to oncogenesis. This highlights the importance of precise splicing in maintaining cellular health.</span

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Key Concepts

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

RNA Splicing

RNA splicing is a crucial process in gene expression where introns (non-coding regions) are removed from pre-mRNA, and exons (coding regions) are joined together. This process allows for the production of mature mRNA that can be translated into proteins. Errors in splicing can lead to the production of dysfunctional proteins, which may disrupt normal cellular functions and contribute to diseases, including cancer.
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Tumor-Suppressor Genes

Tumor-suppressor genes are critical for regulating cell growth and preventing uncontrolled cell division. They produce proteins that help repair DNA, control the cell cycle, and promote apoptosis (programmed cell death). When these genes are mutated or their function is disrupted, it can lead to the development of tumors, as the normal checks on cell proliferation are lost.
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Splicing Specificity and Cancer

Splicing specificity refers to the precise selection of splice sites during RNA processing, ensuring that the correct mRNA isoforms are produced. Loss of splicing specificity can result in aberrant splicing patterns, leading to the production of non-functional or harmful protein variants. This dysregulation is often associated with cancer, as it can affect the expression and function of tumor-suppressor genes, contributing to tumorigenesis.
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Cancer Characteristics
Related Practice
Textbook Question

Regulation of the lac operon in E. coli (see Chapter 16) and regulation of the GAL system in yeast are analogous in that they both serve to adapt cells to growth on different carbon sources. However, the transcriptional changes are accomplished very differently. Consider the conceptual similarities and differences as you address the following.

Compare and contrast the roles of the lac operon inducer in bacteria and Gal3p in eukaryotes in the regulation of their respective systems.

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Textbook Question

Regulation of the lac operon in E. coli (see Chapter 16) and regulation of the GAL system in yeast are analogous in that they both serve to adapt cells to growth on different carbon sources. However, the transcriptional changes are accomplished very differently. Consider the conceptual similarities and differences as you address the following.

Compare and contrast the cis-regulatory elements of the lac operon and GAL gene system.

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Textbook Question

Regulation of the lac operon in E. coli (see Chapter 16) and regulation of the GAL system in yeast are analogous in that they both serve to adapt cells to growth on different carbon sources. However, the transcriptional changes are accomplished very differently. Consider the conceptual similarities and differences as you address the following.

Compare and contrast how these two systems are negatively regulated such that they are downregulated in the presence of glucose.

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Textbook Question

Mutations in the low-density lipoprotein receptor (LDLR) gene are a primary cause of familial hypercholesterolemia. One such mutation is a SNP in exon 12 of the LDLR. In premenopausal women, but not in men or postmenopausal women, this SNP leads to skipping of exon 12 and production of a truncated nonfunctional protein. It is hypothesized that this SNP compromises a splice enhancer [Zhu et al. (2007). Hum Mol Genet. 16:1765–1772]. What are some possible ways in which this SNP can lead to this defect, but only in premenopausal women?

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Textbook Question

During an examination of the genomic sequences surrounding the human β-globin gene, you discover a region of DNA that bears sequence resemblance to the glucocorticoid response element (GRE) of the human metallothionein IIA (hMTIIA) gene. Describe experiments that you would design to test (1) whether this sequence was necessary for accurate β-globin gene expression and (2) whether this sequence acted in the same way as the hMTIIA gene's GRE.

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Textbook Question

RNA helicases are a class of proteins that bind mRNAs and influence their secondary structures and interactions with other proteins. RNA helicases have been implicated in many steps of RNA regulation such as splicing, decay, and translation. Why might these enzymes be so ubiquitously required for RNA regulation?

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