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Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts
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PABP prevents the untimely decay of select mRNA populations in human cells

Sam Kajjo1,2, Sahil Sharma1,2, Shan Chen3

  • 1Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.

The EMBO Journal
|February 14, 2022
PubMed

Insights

Poly(A)-binding protein (PABP) primarily safeguards mRNA stability, not translation, in human cells. PABP depletion destabilizes essential transcripts, leading to cell death partially mediated by mRNA decay pathways.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Cell Biology

Background:

  • Gene expression relies on mRNA translation and stability.
  • Poly(A)-binding protein (PABP) binds mRNA 3' poly(A) tails, potentially regulating translation and decay.
  • PABP's precise role in endogenous mRNA regulation in human cells requires direct investigation.

Purpose of the Study:

  • To investigate the direct impact of PABP on endogenous mRNA translation and stability in human cells.
  • To elucidate PABP's role in mRNA decay pathways and PABP depletion-induced cell death.

Main Methods:

  • Transcriptome-wide analysis of mRNA translation and stability.
  • PABP depletion in human cells.
  • Investigation of mRNA decay machinery components (e.g., decapping, 5'-3' decay, LSM1-7 complex).

Main Results:

  • PABP depletion caused minimal changes in global mRNA translation.
  • Rapid PABP depletion significantly altered mRNA abundance and stability, destabilizing otherwise stable transcripts.
  • PABP depletion-induced cell death was partially rescued by inhibiting mRNA decapping and 5'-3' decay.
  • The LSM1-7 complex was implicated in the decay of stable mRNAs upon PABP depletion.

Conclusions:

  • PABP plays a crucial role in preventing the premature decay of specific mRNA populations.
  • PABP's primary function in human cells appears to be maintaining mRNA stability rather than regulating translation.
  • These findings highlight PABP's critical role in cellular homeostasis by safeguarding essential transcripts.
Keywords:
P-bodiesPABPmRNA decappingmRNA decaymRNA translation

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