A Regulatory Response to Ribosomal Protein Mutations Controls Translation, Growth, and Cell Competition

Chang Hyun Lee, Marianthi Kiparaki, Jorge Blanco, Virginia Folgado, Zhejun Ji, Amit Kumar, Gerard Rimesso, Nicholas E. Baker

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Ribosomes perform protein synthesis but are also involved in signaling processes, the full extent of which are still being uncovered. We report that phenotypes of mutating ribosomal proteins (Rps) are largely due to signaling. Using Drosophila, we discovered that a bZip-domain protein, Xrp1, becomes elevated in Rp mutant cells. Xrp1 reduces translation and growth, delays development, is responsible for gene expression changes, and causes the cell competition of Rp heterozygous cells from genetic mosaics. Without Xrp1, even cells homozygously deleted for Rp genes persist and grow. Xrp1 induction in Rp mutant cells depends on a particular Rp with regulatory effects, RpS12, and precedes overall changes in translation. Thus, effects of Rp mutations, even the reductions in translation and growth, depend on signaling through the Xrp1 pathway and are not simply consequences of reduced ribosome production limiting protein synthesis. One benefit of this system may be to eliminate Rp-mutant cells by cell competition. Certain mutant cells are eliminated only in mosaic tissues. Lee et al. isolate mutations in a bZip-domain protein, Xrp1, that rescue ribosomal protein (Rp) heterozygous mutant cells from such competition. Xrp1 accounts for many aspects of the Rp mutant phenotype, indicating they are not direct consequences of ribosome depletion.

Original languageEnglish (US)
Pages (from-to)456-469.e4
JournalDevelopmental cell
Volume46
Issue number4
DOIs
StatePublished - Aug 20 2018

Keywords

  • Drosophila development
  • Xrp1
  • cell competition
  • growth regulation
  • minute mutation
  • regulation of translation
  • ribosomal protein
  • ribosomopathy

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A Regulatory Response to Ribosomal Protein Mutations Controls Translation, Growth, and Cell Competition'. Together they form a unique fingerprint.

  • Cite this