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Updated: Oct 10, 2025

Measurement of mRNA Decay Rates in Saccharomyces cerevisiae Using rpb1-1 Strains
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Cellular variability of nonsense-mediated mRNA decay

Hanae Sato1, Robert H Singer2,3,4

  • 1Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY, 10461, USA.

Nature Communications
|December 11, 2021
PubMed

Insights

Nonsense-mediated mRNA decay (NMD) efficiency varies greatly between individual cells. This study reveals cell-to-cell differences in NMD surveillance factors, leading to mRNA escape via readthrough or failed degradation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Nonsense-mediated mRNA decay (NMD) is a crucial cellular surveillance pathway.
  • NMD eliminates messenger RNAs (mRNAs) harboring premature termination codons (PTCs).
  • The variability in NMD efficiency at the single-cell level remains poorly understood.

Purpose of the Study:

  • To investigate the heterogeneity of NMD efficiency in individual cells.
  • To identify the molecular mechanisms underlying NMD escape.
  • To correlate NMD efficiency with the levels of key NMD regulators.

Main Methods:

  • Development of a single-cell bi-directional reporter system for NMD analysis.
  • Utilizing flow cytometry to quantify NMD efficiency in single cells.
  • Assessing the expression levels of NMD factors like SMG1 and phosphorylated UPF1.

Main Results:

  • Demonstrated a wide spectrum of NMD efficiencies across a cell population.
  • Identified cell-to-cell variability in NMD efficiency, ranging from complete degradation to near-complete escape.
  • Linked NMD efficiency variability to differential expression of SMG1 and phosphorylated UPF1.
  • Discovered NMD escape mechanisms including translational readthrough and post-termination mRNA degradation failure.

Conclusions:

  • Cellular NMD efficiency is highly heterogeneous, not uniform.
  • Variability in NMD surveillance factors drives differential mRNA decay rates.
  • Single-cell analysis provides critical insights into NMD regulation and escape mechanisms.

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