Ribosomal protein mutations and cell competition: autonomous and nonautonomous effects on a stress response.
Ribosomal protein mutations and cell competition: autonomous and nonautonomous effects on a stress response.
复制标题
核糖体蛋白突变和细胞竞争：对应激反应的自主和非自主影响。
DOI：
10.1093/genetics/iyad080
复制
发表时间：
2023
期刊：
影响因子：
3.3
通讯作者：
Baker,NicholasE
中科院分区：
文献类型：
--
作者：
Kiparaki,Marianthi;Baker,NicholasE
Ribosomal proteins (Rps) are essential for viability. Genetic mutations affecting Rp genes were first discovered inDrosophila, where they represent a major class of haploinsufficient mutations. One mutant copy gives rise to the dominant “Minute” phenotype, characterized by slow growth and small, thin bristles. Wild-type (WT) and Minute cells compete in mosaics, that is,Rp+/−are preferentially lost when their neighbors are of the wild-type genotype. Many features of Rp gene haploinsufficiency (i.e.Rp+/−phenotypes) are mediated by a transcriptional program. InDrosophila, reduced translation and slow growth are under the control of Xrp1, a bZip-domain transcription factor induced inRpmutant cells that leads ultimately to the phosphorylation of eIF2α and consequently inhibition of most translation.Rpmutant phenotypes are also mediated transcriptionally in yeast and in mammals. In mammals, the Impaired Ribosome Biogenesis Checkpoint activates p53. Recent findings linkRpmutant phenotypes to other cellular stresses, including the DNA damage response and endoplasmic reticulum stress. We suggest that cell competition results from nonautonomous inputs to stress responses, bringing decisions between adaptive and apoptotic outcomes under the influence of nearby cells. InDrosophila, cell competition eliminates aneuploid cells in which loss of chromosome leads to Rp gene haploinsufficiency. The effects of Rp gene mutations on the whole organism, in Minute flies or in humans with Diamond-Blackfan Anemia, may be inevitable consequences of pathways that are useful in eliminating individual cells from mosaics. Alternatively, apparently deleterious whole organism phenotypes might be adaptive, preventing even more detrimental outcomes. In mammals, for example, p53 activation appears to suppress oncogenic effects of Rp gene haploinsufficiency.
