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Ch. 18 - Post-transcriptional Regulation in Eukaryotes
Klug - Concepts of Genetics 12th Edition
Klug12th EditionConcepts of Genetics ISBN: 9780135564776Not the one you use?Change textbook
All textbooksKlug 12th EditionCh. 18 - Post-transcriptional Regulation in EukaryotesProblem 28
Chapter 18, Problem 28

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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1
Understand that miRNA response elements (MREs) are sequences within mRNA that miRNAs bind to in order to regulate gene expression, typically by repressing translation or promoting mRNA degradation.
Recognize that the coding region of mRNA encodes the protein sequence, so it is under strong evolutionary pressure to maintain its sequence to preserve protein function.
Consider that the 5' and 3' untranslated regions (UTRs) do not code for protein but can contain regulatory elements, making them more flexible regions for miRNA binding without disrupting protein coding.
Since miRNAs often target multiple mRNAs, having MREs in the UTRs allows for conserved regulatory sequences that can be shared across different mRNAs without affecting the protein sequences encoded by the coding regions.
Conclude that locating MREs in the UTRs facilitates coordinated regulation of multiple mRNAs by miRNAs while preserving the integrity of the protein-coding sequences.

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Key Concepts

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

miRNA Function and Targeting

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to complementary sequences on target mRNAs, usually leading to mRNA degradation or translational repression. Their ability to target multiple mRNAs depends on recognizing specific sequences called miRNA response elements (MREs), which guide the miRNA to its targets.
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Untranslated Regions (UTRs) of mRNA

The 5' and 3' untranslated regions (UTRs) of mRNA are non-coding sequences flanking the coding region. These regions often contain regulatory elements, including MREs, that influence mRNA stability and translation without altering the protein sequence, making them ideal sites for miRNA binding.
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Conservation and Flexibility of miRNA Target Sites

MREs located in UTRs allow miRNAs to regulate multiple mRNAs efficiently because UTR sequences are less constrained by protein-coding requirements, enabling conserved binding sites across different transcripts. This flexibility facilitates broad post-transcriptional regulation without disrupting protein function.
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Related Practice
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

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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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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Textbook Question

Explain how the expression of a single gene can be quickly, efficiently, and specifically shut down at the transcriptional, posttranscriptional, and posttranslational stages through the coordinated expression of a transcriptional repressor, an miRNA, and a ubiquitin ligase.

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