miRNAs target endogenous mRNAs in a sequence-specific manner. Explain, conceptually, how one might identify potential mRNA targets for a given miRNA if you only know the sequence of the miRNA and the sequence of all mRNAs in a cell or tissue of interest.
Table of contents
- 1. Introduction to Genetics51m
- 2. Mendel's Laws of Inheritance3h 37m
- 3. Extensions to Mendelian Inheritance2h 41m
- 4. Genetic Mapping and Linkage2h 28m
- 5. Genetics of Bacteria and Viruses1h 21m
- 6. Chromosomal Variation1h 48m
- 7. DNA and Chromosome Structure56m
- 8. DNA Replication1h 10m
- 9. Mitosis and Meiosis1h 34m
- 10. Transcription1h 0m
- 11. Translation58m
- 12. Gene Regulation in Prokaryotes1h 19m
- 13. Gene Regulation in Eukaryotes44m
- 14. Genetic Control of Development44m
- 15. Genomes and Genomics1h 50m
- 16. Transposable Elements47m
- 17. Mutation, Repair, and Recombination1h 6m
- 18. Molecular Genetic Tools19m
- 19. Cancer Genetics29m
- 20. Quantitative Genetics1h 26m
- 21. Population Genetics50m
- 22. Evolutionary Genetics29m
10. Transcription
RNA Interference
Problem 31
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.

1
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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