Ribosomal protein imbalance launches a C/EBP-based program to preserve tissue integrity

Abstract

Genes encoding ribosomal proteins are expressed at rate limiting levels, rendering their biological function highly sensitive to the copy-number variation that results from genomic instability. Cells with a reduced number of ribosomal protein genes (RPGs) are eliminated, when intermingled with wild type cells, via a process known as cell competition. The mechanisms underlying this phenomenon are poorly understood. Here we report the function of a CCAAT-Enhancer-Binding Protein (C/EBP), Xrp1, that is critically required for the elimination of cells with a hemizygous RPG genotype. In such cells, Xrp1 is transcriptionally upregulated by an autoregulatory loop and is able to trigger cell elimination. Since genomic instability is likely to cause the loss of a haploinsufficient RPG, we propose a molecular model of how RPGs, together with a C/EBP-dependent transcriptional program, could preserve the genomic integrity of tissues.