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Related Concept Videos

Regulation of Expression at Multiple Steps01:23

Regulation of Expression at Multiple Steps

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene expression can be regulated at almost every step from gene to protein. Transcription is the step that is most commonly regulated. This involves the binding of proteins to short regulatory sequences on the DNA. This association can either promote or inhibit the transcription of a gene associated with the respective sequence.
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General Transcription Factors01:30

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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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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
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Control of Transcript Variability in Single Mammalian Cells.

Nico Battich1, Thomas Stoeger1, Lucas Pelkmans2

  • 1Faculty of Sciences, Institute of Molecular Life Sciences, University of Zurich, 8006 Zurich, Switzerland; Systems Biology PhD Program, Life Science Zurich Graduate School, ETH Zurich and University of Zurich, 8057 Zurich, Switzerland.

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Summary

Cellular variability is mostly predictable, not random. Nuclear processes buffer gene expression noise, ensuring cytoplasmic transcript abundance stability in human cells.

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Area of Science:

  • Cellular and Molecular Biology
  • Genomics
  • Systems Biology

Background:

  • Understanding cell-to-cell variability is crucial for biology.
  • Distinguishing stochasticity from deterministic factors in gene expression is a key challenge.

Purpose of the Study:

  • To investigate the sources of variability in cytoplasmic transcript abundance in single human cells.
  • To determine the extent to which this variability is stochastic versus predictable.

Main Methods:

  • Utilized image-based transcriptomics on millions of single human cells.
  • Developed multivariate models integrating phenotypic state and population context.
  • Employed computational multiplexing for analyzing hundreds of genes.
  • Performed mathematical modeling and experimental validation.

Main Results:

  • Cytoplasmic transcript abundance variability is large but minimally stochastic for most genes.
  • Predictive models incorporating cell state and context accurately forecast transcript levels.
  • A complex regulatory system governs transcript abundance variability.
  • Nuclear retention and transport of transcripts buffer transcriptional noise.

Conclusions:

  • Cellular compartmentalization, specifically within the nucleus, is critical for buffering gene expression noise.
  • This nuclear buffering prevents cytoplasmic transcriptional noise from impacting single-cell transcript abundance control.
  • Variability in gene expression is largely deterministic and predictable based on cellular state.