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Related Concept Videos

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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Bacterial Transcription01:53

Bacterial Transcription

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RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
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General Transcription Factors01:30

General Transcription Factors

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Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
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Transcription01:17

Transcription

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Transcription is the synthesis of RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in correctly synthesizing messenger RNA (mRNA). Transcriptional regulation is responsible for the differentiation of different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds of RNA Molecules
In eukaryotes,...
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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.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
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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.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
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Structural visualization of transcription initiation in action.

Xizi Chen1,2, Weida Liu1, Qianmin Wang1

  • 1Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, New Cornerstone Science Laboratory, State Key Laboratory of Genetic Engineering, Department of Biochemistry and Biophysics, School of Life Sciences, Shanghai Key Laboratory of Radiation Oncology, and Shanghai Key Laboratory of Medical Epigenetics, Shanghai Medical College of Fudan University, Shanghai 200032, China.

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|December 21, 2023
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Summary

This study reveals the dynamic process of transcription initiation by RNA polymerase II. It shows how general transcription factors (GTFs) are essential for early RNA synthesis but must dissociate for promoter escape.

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Transcription initiation is a fundamental biological process.
  • The precise mechanism of transcription initiation, particularly the transition from initiation to elongation, remains incompletely understood.
  • RNA polymerase II transcribes protein-coding genes, and its regulation is crucial for gene expression.

Purpose of the Study:

  • To elucidate the dynamic structural changes during transcription initiation.
  • To understand the role of general transcription factors (GTFs) and the transcription bubble in the transition from initiation to elongation.
  • To develop a working model for de novo transcription initiation by RNA polymerase II.

Main Methods:

  • Determined structures of RNA polymerase II transcribing complexes (TC2 to TC17) at various stages of nascent RNA synthesis (2 to 17 nucleotides).
  • Utilized cryo-electron microscopy or X-ray crystallography to capture static snapshots of dynamic intermediates.
  • Integrated structural data to generate a time-resolved 'movie' of transcription initiation.

Main Results:

  • Observed that general transcription factors (GTFs) remain bound to the promoter as the nascent RNA grows.
  • Documented the expansion of the transcription bubble during initial RNA synthesis.
  • Identified nucleoside triphosphate (NTP)-driven RNA-DNA translocation and template-strand accumulation as potential drivers for the transition from initially transcribing complexes (ITCs) to early elongation complexes (EECs).

Conclusions:

  • Initially transcribing complexes (ITCs) require GTFs and an expanded transcription bubble for initial RNA synthesis.
  • Early elongation complexes (EECs) necessitate GTF dissociation from the promoter and transcription bubble collapse for promoter escape.
  • The study provides a dynamic model for transcription initiation, highlighting key transitions and factor requirements.