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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.
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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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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.
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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Deciphering HIV-1 Transcription Initiation and Elongation from Single-Molecule Imaging Data.

Xiyan Yang1, Zihao Wang2,3, Changhong Shi4

  • 1School of Financial Mathematics and Statistics, Guangdong University of Finance, Guangzhou 510521, P. R. China.

Research (Washington, D.C.)
|December 12, 2025
PubMed
Summary

This study introduces a new model to understand HIV-1 transcription dynamics. The findings reveal how Tat protein influences viral reactivation and latency, potentially improving HIV-1 cure strategies.

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Area of Science:

  • Molecular Biology
  • Computational Biology
  • Virology

Background:

  • HIV-1 gene expression relies on transcription initiation and elongation.
  • Single-molecule imaging reveals HIV-1 transcription occurs over multiple timescales, impacting latency.
  • Current understanding of HIV-1 transcription mechanisms is limited by a lack of unified modeling and advanced computational analysis.

Purpose of the Study:

  • To develop a general stochastic model for HIV-1 transcription dynamics.
  • To create a statistical inference method integrating initiation-time and nascent RNA data.
  • To elucidate the molecular mechanisms of HIV-1 transcription and the role of Tat.

Main Methods:

  • Developed a general stochastic model to characterize HIV-1 transcription dynamics.
  • Computed distributions of initiation times and nascent RNA counts.
  • Created a statistical inference method integrating initiation-time and nascent RNA data.

Main Results:

  • Coordination between initiation and elongation modulates HIV-1 transcription.
  • Leveraging initiation-time data significantly enhances model identification.
  • The developed inference method accurately estimates initiation rate and elongation time, independent of model choice.
  • Tat protein plays a dual role in HIV-1 transcriptional regulation.
  • Tat alters promoter silent states, inducing viral reactivation and latency exit.

Conclusions:

  • The new modeling and inference framework accurately characterizes HIV-1 transcription dynamics.
  • Initiation-time data is crucial for precise parameter estimation in HIV-1 transcription models.
  • Tat's regulation of promoter states is key to HIV-1 reactivation and latency.
  • This approach offers potential improvements for HIV-1 cure strategies.