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.
Bibliographical noteFunding Information:
NEB received awards GM104213 & GM120451 from the National Institutes of General Medical Sciences (https://www.nigms.nih.gov/), and from the Albert Einstein College of Medicine Human Genetics Program. The Bloomington Drosophila Stock Center was supported by NIH (P40OD018537). The Analytical Imaging Facility, Albert Einstein College of Medicine, was supported by NCI (P30CA013330) and by NIH (SIG 1S10 OD023591). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This paper is dedicated to the memory of our colleague Dr. J. Warner. The authors also thank D. Rio for anti-Xrp1 antibody and J. Secombe and C. Khan for comments on the manuscript. Drosophila strains from the Bloomington Drosophila Stock Center were used in this study. Confocal Imaging was performed at the Analytical Imaging Facility, Albert Einstein College of Medicine. This paper includes data from theses partially fulfilling of the requirements for the Degree of Doctor of Philosophy in the Graduate Division of Medical Sciences, Albert Einstein College of Medicine, Yeshiva University.
© 2019 Ji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.