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Related Concept Videos

Genetic Screens02:46

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...

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Multimodal screen identifies noise-regulatory proteins.

Óscar García-Blay1, Xinyu Hu1, Christin L Wassermann2

  • 1Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands; Oncode Institute, Nijmegen, the Netherlands.

Developmental Cell
|October 15, 2024
PubMed
Summary

Scientists discovered proteins that regulate gene expression noise independently of mean expression levels. SON protein controls transcriptional noise, impacting cell fate decisions without altering average gene activity.

Keywords:
SONcell fate choicedifferentiationembryonic stem cellsgene-expression variabilitymRNA processingnoise regulationsingle-cell transcriptomicsstochastic noise

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Area of Science:

  • Cellular biology
  • Molecular biology
  • Genomics

Background:

  • Gene expression noise influences cell-fate decisions in various biological contexts.
  • A key question is whether regulatory proteins control noise independently of mean expression.

Purpose of the Study:

  • Identify regulatory proteins controlling gene expression noise independently of mean expression levels.
  • Investigate the function of identified regulators in cellular processes.

Main Methods:

  • Integrative approach combining single-cell RNA sequencing, proteomics, and regulator enrichment analysis.
  • Utilized long-read and total RNA sequencing.
  • Depletion studies in pluripotent mouse embryonic stem cells.

Main Results:

  • Identified 32 putative noise regulators.
  • SON, a nuclear speckle-associated protein, was found to alter transcriptional noise without affecting mean expression.
  • SON's noise control impacts protein levels and reduces state switching in pluripotent stem cells, influencing differentiation.
  • SON's regulation does not significantly alter isoform usage or splicing efficiency.

Conclusions:

  • Demonstrated a class of proteins that control gene expression noise orthogonally to mean expression levels.
  • SON acts as a functional noise regulator impacting cell-state transitions and fate choices.
  • This study provides a framework for identifying additional noise regulators in development and disease.