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Dev Cell. 2018 Aug 20;46(4):456-469.e4. doi: 10.1016/j.devcel.2018.07.003. Epub 2018 Aug 2.

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

Author information

1
Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
2
Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Electronic address: nicholas.baker@einstein.yu.edu.

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.

KEYWORDS:

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

PMID:
30078730
PMCID:
PMC6261318
DOI:
10.1016/j.devcel.2018.07.003
[Indexed for MEDLINE]
Free PMC Article

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