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 27

Chapter 18, Problem 27

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?

Verified step by step guidance

Understand the role of RNA helicases: These enzymes use energy from ATP hydrolysis to unwind or remodel RNA secondary structures, which are critical for RNA function and interactions.

Recognize that RNA molecules often form complex secondary structures (like hairpins and loops) that can influence their stability, localization, and ability to interact with proteins or other RNAs.

Consider that many RNA regulatory processes—such as splicing, decay, and translation—require dynamic changes in RNA structure to allow access to specific sites or to facilitate the assembly/disassembly of RNA-protein complexes.

Realize that RNA helicases are ubiquitously required because they enable these structural rearrangements, ensuring that RNA molecules can properly undergo processing, be translated efficiently, or be degraded when necessary.

Conclude that without RNA helicases, the RNA secondary structures might remain static or improperly folded, hindering essential regulatory steps and thus affecting overall gene expression.

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Key Concepts

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

RNA Secondary Structure

RNA molecules can fold into complex secondary structures like hairpins and loops, which influence their stability and interactions. RNA helicases unwind or remodel these structures, enabling proper RNA processing and function.

Role of RNA Helicases in RNA Metabolism

RNA helicases use energy from ATP hydrolysis to alter RNA conformations, facilitating processes such as splicing, decay, and translation by resolving RNA-protein complexes and remodeling RNA structures.

Regulation of Gene Expression at the RNA Level

RNA regulation involves multiple steps controlling RNA maturation, localization, translation, and degradation. RNA helicases are essential because they enable dynamic changes in RNA structure necessary for these regulatory mechanisms.

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Related Practice

Textbook Question

We discussed several specific cis-elements in mRNAs that regulate splicing, stability, decay, localization, and translation. However, it is likely that many other uncharacterized cis-elements exist. One way in which they may be characterized is through the use of a reporter gene such as the gene encoding the green fluorescent protein (GFP) from jellyfish. GFP emits green fluorescence when excited by blue light. Explain how one might be able to devise an assay to test for the effect of various cis-elements on posttranscriptional gene regulation using cells that transcribe a GFP mRNA with genetically inserted cis-elements.

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Textbook Question

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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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

While miRNA response elements (MREs) may be located anywhere within an mRNA, they are most often found outside the coding region in the 5' or 3' UTR. Explain why this is likely the case given that miRNAs often target more than one mRNA.

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Textbook Question

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.

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Textbook Question

The localization and translational control of actin mRNA is important for the migration of fibroblasts and is regulated by the activity of the kinase Src. Src is activated by phosphorylation when cell surface receptors bind to signaling molecules. How might this system lead to a cell migrating in a specific direction? How might the cell migrate away from repulsive signals?

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