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Related Concept Videos

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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Master Transcription Regulators02:23

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Eukaryotic Transcription Activators02:42

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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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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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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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Transcription Initiation01:47

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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.
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Related Experiment Video

Updated: Aug 15, 2025

A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers
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A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers

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THOC5 complexes with DDX5, DDX17, and CDK12 to regulate R loop structures and transcription elongation rate.

Mareike Polenkowski1,2, Aldrige Bernardus Allister1,3, Sebastian Burbano de Lara4

  • 1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover D-30623, Germany.

Iscience
|January 2, 2023
PubMed
Summary

THOC5 protein depletion alters mRNA processing and significantly slows transcription elongation. This protein interacts with CDK12 and RNA helicases, revealing a novel role in regulating gene expression.

Keywords:
Cell biologyMolecular biology

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cell Biology

Background:

  • THOC5 is a component of the THO complex.
  • It plays roles in mRNA 3' processing, export, and stem cell survival.

Purpose of the Study:

  • To investigate the function of THOC5 in transcription.
  • To elucidate the mechanisms by which THOC5 influences gene expression.

Main Methods:

  • THOC5 depletion using RNA interference.
  • Analysis of mRNA 3' cleavage and RNA polymerase II binding.
  • Measurement of in vivo transcription elongation rates.
  • Co-immunoprecipitation assays to study protein interactions.

Main Results:

  • THOC5 depletion altered 3' cleavage of over 50% of mRNAs.
  • THOC5 depletion decreased transcription elongation rates.
  • THOC5 interacts with CDK12, DDX5, DDX17, and THOC6 in slow polymerase II cells.
  • The CDK12/THOC5 interaction promotes CDK12 recruitment to R-loops.

Conclusions:

  • THOC5 plays a crucial role in transcription elongation.
  • THOC5 functions in concert with CDK12 and RNA helicases to regulate gene expression.
  • These findings reveal a novel mechanism for THOC5 in controlling transcriptional processes.