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

Elife. 2022 Feb 18;11:e71705. doi: 10.7554/eLife.71705.


Ribosomal Protein (Rp) gene haploinsufficiency affects translation rate, can lead to protein aggregation, and causes cell elimination by competition with wild type cells in mosaic tissues. We find that the modest changes in ribosomal subunit levels observed were insufficient for these effects, which all depended on the AT-hook, bZip domain protein Xrp1. Xrp1 reduced global translation through PERK-dependent phosphorylation of eIF2α. eIF2α phosphorylation was itself sufficient to enable cell competition of otherwise wild type cells, but through Xrp1 expression, not as the downstream effector of Xrp1. Unexpectedly, many other defects reducing ribosome biogenesis or function (depletion of TAF1B, eIF2, eIF4G, eIF6, eEF2, eEF1α1, or eIF5A), also increased eIF2α phosphorylation and enabled cell competition. This was also through the Xrp1 expression that was induced in these depletions. In the absence of Xrp1, translation differences between cells were not themselves sufficient to trigger cell competition. Xrp1 is shown here to be a sequence-specific transcription factor that regulates transposable elements as well as single-copy genes. Thus, Xrp1 is the master regulator that triggers multiple consequences of ribosomal stresses and is the key instigator of cell competition.

Keywords: D. melanogaster; cell biology; cell competition; copia; developmental biology; ribosomal protein; ribosome; ribosomopathy; translation; xrp1 gene.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Competition*
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Eukaryotic Initiation Factor-2 / metabolism
  • Phosphorylation
  • Protein Biosynthesis
  • Ribosomes / metabolism
  • Transcription Factors / metabolism


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Eukaryotic Initiation Factor-2
  • TAF1B protein, Drosophila
  • Transcription Factors
  • Xrp1 protein, Drosophila

Associated data

  • GEO/GSE112864
  • GEO/GSE124924