DrosophilaRpS12 controls translation, growth, and cell competition through Xrp1.

Zhejun Ji,Jacky Chuen,Gerard Rimesso,Deyou Zheng,Virginia Folgado,Nicholas E Baker,Amit Kumar,Jorge Blanco,Marianthi Kiparaki,Yang Liu,Tin Tin Su

doi:10.1371/journal.pgen.1008513

Abstract

Whereas complete loss of Rp function is generally lethal, most heterozygous Rp mutants grow more slowly and are subject to competitive loss from mosaics tissues that also contain wild type cells. The rpS12 gene has a special role in the cell competition of other Ribosomal Protein (Rp) mutant cells in Drosophila. Elimination by cell competition is promoted by higher RpS12 levels and prevented by a specific rpS12 mis-sense mutation, identifying RpS12 as a key effector of cell competition due to mutations in other Rp genes. Here we show that RpS12 is also required for other aspects of Rp mutant phenotypes, including hundreds of gene expression changes that occur in ‘Minute’ Rp heterozygous wing imaginal discs, overall translation rate, and the overall rate of organismal development, all through the bZip protein Xrp1 that is one of the RpS12-regulated genes. Our findings outline the regulatory response to mutations affecting essential Rp genes that controls overall translation, growth, and cell competition, and which may contribute to cancer and other diseases.

Highlights

Around 80 of the many proteins that interact with eukaryotic rRNA during ribosome biogenesis are stably associated with the mature ribosomal Large or Small Subunits [1]
Mutations in Ribosomal protein (Rp) genes affect translation but they are involved in human diseases and in cancer for reasons that are not yet clear
Frequent ribosomal proteins (Rp) point mutations occur in T-cell Acute Lymphoblastic Leukemia (T-ALL), Chronic Lymphocytic Leukemia (CLL), and colon cancer

Summary

Introduction

Around 80 of the many proteins that interact with eukaryotic rRNA during ribosome biogenesis are stably associated with the mature ribosomal Large or Small Subunits [1]. Most of these ribosomal proteins (Rp) are essential to the cell, with roles in ribosome biogenesis and/or in the function of the mature ribosomes. The full spectrum of Rp function is far from understood, as illustrated by the recurrent observation of Rp mutations in cancers. Frequent Rp point mutations occur in T-cell Acute Lymphoblastic Leukemia (T-ALL), Chronic Lymphocytic Leukemia (CLL), and colon cancer. It seems paradoxical that positive regulators of translation behave like tumor suppressors

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