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

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.