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Related Concept Videos

Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

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Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
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Initiation of Translation02:33

Initiation of Translation

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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
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Transcription Elongation Factors02:35

Transcription Elongation Factors

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Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
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Eukaryotic Transcription Inhibitors01:52

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Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
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Transcription Initiation01:47

Transcription Initiation

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Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
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Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

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RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
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E2F1-3 activate Merkel cell polyomavirus early transcription and replication.

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Merkel cell polyomavirus (MCPyV) Large and Small Tumor antigens (LT, ST) expression is controlled by E2F transcription factors binding to the viral NCCR. This reveals a feedback loop crucial for viral replication and Merkel cell carcinoma (MCC) development.

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Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry
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Area of Science:

  • Virology
  • Oncology
  • Molecular Biology

Background:

  • Merkel cell polyomavirus (MCPyV) causes Merkel cell carcinoma (MCC).
  • MCPyV Large and Small Tumor antigens (LT, ST) drive viral replication and tumorigenesis.
  • Control mechanisms for MCPyV LT/ST expression are poorly understood.

Purpose of the Study:

  • To elucidate the regulatory mechanisms controlling MCPyV LT/ST expression.
  • To investigate the role of E2F transcription factors in MCPyV early gene regulation.
  • To understand the implications for viral replication and MCC pathogenesis.

Main Methods:

  • Identified E2F1-3/DP1 binding to the MCPyV Non-Coding Control Region (NCCR) using a consensus E2 site.
  • Utilized E2 site deletion and small molecule inhibitors to block E2F-NCCR interaction.
  • Assessed LT/ST mRNA and protein expression in MCC and transfected cells.

Main Results:

  • E2F1-3/DP1 dimers bind the MCPyV NCCR at a specific E2 site.
  • Inhibition of E2F-NCCR binding downregulates MCPyV LT/ST expression.
  • Identified similar E2 sites in related polyomaviruses, suggesting conserved regulatory mechanisms.

Conclusions:

  • Discovered an E2F/LT/RB1 positive feedback loop essential for MCPyV replication and MCC proliferation.
  • Challenged the model that PyV LT drives S phase entry; instead, S phase entry stimulates PyV early transcription.
  • E2F-mediated regulation is a conserved mechanism in related polyomaviruses.