Drosophila RpS12 controls translation, growth, and cell competition through Xrp1
| Autor: | Jorge Blanco, Marianthi Kiparaki, Nicholas E. Baker, Amit Kumar, Deyou Zheng, Virginia Folgado, Zhejun Ji, Jacky Chuen, Gerard Rimesso, Yang Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Cancer Research Mutant Gene Expression QH426-470 medicine.disease_cause Biochemistry 0302 clinical medicine Morphogenesis Drosophila Proteins Genetics (clinical) Regulation of gene expression 0303 health sciences Mutation Effector Messenger RNA Gene Expression Regulation Developmental Cell biology DNA-Binding Proteins Nucleic acids Drosophila melanogaster Imaginal Discs Female Cellular Structures and Organelles Research Article Ribosomal Proteins Mutation Missense Biology Research and Analysis Methods 03 medical and health sciences medicine Genetics Animals Point Mutation Gene Regulation Molecular Biology Techniques Gene Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Sequence Analysis RNA Point mutation Gene Expression Profiling Wild type Biology and Life Sciences Cell Biology Gene expression profiling Protein Biosynthesis RNA Protein Translation Ribosomes 030217 neurology & neurosurgery Cloning Developmental Biology |
| Zdroj: | PLoS Genetics, Vol 15, Iss 12, p e1008513 (2019) PLoS Genetics |
| ISSN: | 1553-7404 1553-7390 |
| Popis: | 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. Author summary Ribosomes, the cellular machines that synthesizes new proteins, are themselves made of RNA and proteins. Mutations in Ribosomal protein (Rp) genes affect translation but they are also involved in human diseases and in cancer for reasons that are not yet clear. In the fruitfly Drosophila melanogaster, individual cells carrying mutations in Rp genes can be recognized and eliminated from tissues in a process of ‘cell competition’. Two genes that have been found to be required for cell competition include one specific Rp, RpS12 and the putative transcription factor Xrp1. Previous work has suggested that RpS12 was more specific for cell competition than Xrp1, which was also responsible for other aspects of Rp phenotypes such as changes in gene expression profiles, overall translation, and the rate of organismal development. This paper shows that RpS12 in fact controls Xrp1 levels and all the same aspects of the ‘Minute’ Rp heterozygous phenotype. Xrp1 is required for these RpS12 effects, establishing RpS12 as the most upstream component known of the signaling that occurs in Rp mutants. |
| Databáze: | OpenAIRE |
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