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The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome

Marianthi Kiparaki1,2, Chaitali Khan1, Virginia Folgado-Marco1

  • 1Department of Genetics, Albert Einstein College of Medicine, The Bronx, United States.

Elife
|February 18, 2022
PubMed

Insights

Ribosomal protein gene changes cause cell competition, but only when the protein Xrp1 is involved. Xrp1 acts as a master regulator, triggering cell competition through ribosomal stress responses.

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Ribosomal protein (Rp) gene haploinsufficiency impacts translation, protein aggregation, and cell competition in mosaic tissues.
  • Observed changes in ribosomal subunit levels were insufficient to explain these effects.

Purpose of the Study:

  • To investigate the role of the AT-hook, bZip domain protein Xrp1 in ribosomal stress responses and cell competition.
  • To elucidate the mechanism by which ribosomal stress triggers cell competition.

Main Methods:

  • Investigated the effects of Rp gene haploinsufficiency and Xrp1 on translation rates and cell competition.
  • Utilized PERK-dependent phosphorylation of eIF2α as a key molecular marker.
  • Examined the impact of various ribosomal biogenesis and function defects on eIF2α phosphorylation and cell competition.
  • Characterized Xrp1 as a sequence-specific transcription factor.

Main Results:

  • Xrp1, not modest ribosomal subunit changes, was essential for cell competition.
  • Xrp1 reduced global translation via PERK-dependent eIF2α phosphorylation.
  • eIF2α phosphorylation and cell competition were induced by Xrp1 expression, even in cells with defects in ribosome biogenesis or function.
  • Xrp1 acts as a sequence-specific transcription factor regulating transposable elements and single-copy genes.

Conclusions:

  • Xrp1 is the master regulator of ribosomal stress responses and the key instigator of cell competition.
  • Ribosomal stress-induced cell competition is primarily mediated by Xrp1, not solely by translation rate differences.
Keywords:
D. melanogastercell biologycell competitioncopiadevelopmental biologyribosomal proteinribosomeribosomopathytranslationxrp1 gene

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