Abstract 1726 Elucidating the relationship between cytoplasmic ribosomes and mitochondria utilizing gene expression and proportionality

The group of genetic ribosome biogenesis abnormalities known as ribosomopathies result from single copy loss of translation machinery components and are implicated in an array of disease symptoms such as bone marrow failure and anemia. Among four tested ribosomal protein genes to model ribosomopathies in C. elegans, we found that rps-10 single copy loss exhibits a distinct phenotype characterized by reduced oxygen consumption, reduced mitochondrial membrane potential, and depletion of energy as indicated by ATP/ADP ratios. To investigate whether the relationship between RPS10 gene and mitochondrial function is conserved in humans, differential expression and proportionality analysis were employed. RNA-Seq and ribosome profiling of 15 different ribosomal protein knockdowns including RPS10 in human cells was analyzed for differential expression. Furthermore, proportionality data of human expression across 1076 samples was filtered for genes whose expression was highly proportional to RPS10 gene and other ribosomal protein genes. We found a profound connection between gene expression of the majority of ribosome and mitochondria components. The human cell expression results do suggest some avenues for further exploration as differential expression analysis in RPS10 knockdown exhibits enrichment in phosphatase/kinase regulation not seen in other riboprotein knockdowns, and RPS10 demonstrates specific negative proportionality to ETFDH, a protein in the mitochondrial electron-transport system. Taken together, our results suggest a strong correlation between expression of ribosome and mitochondria components and we find that reduction of RPS10 alters mitochondrial function based on C. elegans ribosomopathy model and knockdown experiments in human cells.