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.
Ch. 18 - Post-transcriptional Regulation in Eukaryotes

Chapter 18, Problem 31
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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At the transcriptional level, a transcriptional repressor protein binds to specific DNA sequences near the target gene's promoter region, preventing RNA polymerase from initiating transcription. This effectively shuts down the production of the gene's mRNA by blocking the gene's expression at its source.
At the posttranscriptional level, an miRNA (microRNA) molecule binds complementary sequences on the target mRNA transcript. This binding either promotes degradation of the mRNA or inhibits its translation by ribosomes, reducing the amount of protein produced from the mRNA without altering the DNA.
At the posttranslational level, a ubiquitin ligase enzyme attaches ubiquitin molecules to the target protein, marking it for degradation by the proteasome. This process rapidly removes the protein product after it is made, ensuring that any residual protein is efficiently eliminated.
The coordinated expression of these three regulators allows for a multi-layered control system: the transcriptional repressor prevents new mRNA synthesis, the miRNA reduces existing mRNA stability or translation, and the ubiquitin ligase degrades existing protein. This ensures a quick, efficient, and specific shutdown of the gene's expression at multiple stages.
Together, these mechanisms provide tight regulation by targeting the gene expression pathway at different points, allowing the cell to respond rapidly to environmental or developmental signals by silencing the gene precisely and effectively.

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Key Concepts
Here are the essential concepts you must grasp in order to answer the question correctly.
Transcriptional Repression
Transcriptional repressors are proteins that bind to specific DNA sequences near a gene's promoter to inhibit the initiation of transcription. By blocking RNA polymerase or recruiting chromatin-modifying complexes, they prevent mRNA synthesis, effectively shutting down gene expression at the transcriptional level.
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Eukaryotic Transcription
Posttranscriptional Regulation by miRNA
MicroRNAs (miRNAs) are small non-coding RNAs that bind complementary sequences on target mRNAs, leading to mRNA degradation or translational repression. This mechanism allows rapid and specific downregulation of gene expression after transcription, controlling protein production efficiently.
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Regulation
Posttranslational Regulation via Ubiquitin Ligase
Ubiquitin ligases tag specific proteins with ubiquitin molecules, marking them for degradation by the proteasome. This posttranslational control quickly removes existing proteins, ensuring precise and timely shutdown of gene function at the protein level.
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Related Practice
Textbook Question
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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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