Ch. 16 - Regulation of Gene Expression in Eukaryotes
Chapter 16, Problem 29c
Many viruses that infect eukaryotic cells express genes that alter the regulation of host gene expression to promote viral replication. For example, herpes simplex virus-1 (HSV-1) expresses a protein called ICP0, which is necessary for successful viral infection and replication within the host. Lutz et al. (2017. Viruses 9: 210) showed that ICP0 can act as a ubiquitin ligase and target the redundant transcriptional repressors ZEB1 and ZEB2, which leads to upregulation of the miR-183 cluster (a set of three miRNAs transcribed from the same locus).
Speculate on how miR-183 cluster upregulation may benefit the virus.
Verified step by step guidance1
Step 1: Understand the role of miRNAs in gene regulation. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression post-transcriptionally, usually by binding to target mRNAs and causing their degradation or inhibiting their translation.
Step 2: Recognize that the miR-183 cluster consists of three miRNAs transcribed from the same genetic locus, which can coordinately regulate multiple target genes involved in various cellular processes.
Step 3: Consider that upregulation of the miR-183 cluster by the virus could lead to downregulation of host genes that normally restrict viral replication, such as antiviral response genes or genes involved in apoptosis.
Step 4: Analyze how the viral protein ICP0, by targeting transcriptional repressors ZEB1 and ZEB2 for degradation, indirectly increases miR-183 cluster expression, thereby modulating the host cellular environment to favor viral replication.
Step 5: Speculate that the benefit to the virus includes creating a cellular environment that suppresses host defenses and promotes viral gene expression and replication, through the miR-183 cluster-mediated regulation of host gene networks.
Key Concepts
Here are the essential concepts you must grasp in order to answer the question correctly.
MicroRNA (miRNA) Function and Gene Regulation
MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally by binding to target mRNAs, leading to their degradation or translational repression. The miR-183 cluster, consisting of three co-transcribed miRNAs, can modulate multiple host genes simultaneously, influencing cellular pathways such as immune response, apoptosis, and cell cycle control.
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Viral Manipulation of Host Gene Expression
Viruses often alter host gene expression to create a cellular environment favorable for their replication. By expressing proteins like ICP0 that degrade host transcriptional repressors, viruses can upregulate specific host genes or miRNAs, thereby suppressing antiviral defenses or promoting cell survival to enhance viral replication.
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Ubiquitin-Mediated Protein Degradation
Ubiquitin ligases tag specific proteins with ubiquitin molecules, marking them for degradation by the proteasome. ICP0 acts as a ubiquitin ligase targeting repressors ZEB1 and ZEB2, removing their inhibitory effect on the miR-183 cluster, which leads to increased miRNA expression and downstream effects beneficial to viral infection.
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