Cell autonomous and non-autonomous consequences of deviations in translation machinery on organism growth and the connecting signalling pathways.
Agustian SuryaElif Sarinay CenikPublished in: Open biology (2022)
Translation machinery is responsible for the production of cellular proteins; thus, cells devote the majority of their resources to ribosome biogenesis and protein synthesis. Single-copy loss of function in the translation machinery components results in rare ribosomopathy disorders, such as Diamond-Blackfan anaemia in humans and similar developmental defects in various model organisms. Somatic copy number alterations of translation machinery components are also observed in specific tumours. The organism-wide response to haploinsufficient loss-of-function mutations in ribosomal proteins or translation machinery components is complex: variations in translation machinery lead to reduced ribosome biogenesis, protein translation and altered protein homeostasis and cellular signalling pathways. Cells are affected both autonomously and non-autonomously by changes in translation machinery or ribosome biogenesis through cell-cell interactions and secreted hormones. We first briefly introduce the model organisms where mutants or knockdowns of protein synthesis and ribosome biogenesis are characterized. Next, we specifically describe observations in Caenorhabditis elegans and Drosophila melanogaster , where insufficient protein synthesis in a subset of cells triggers cell non-autonomous growth or apoptosis responses that affect nearby cells and tissues. We then cover the characterized signalling pathways that interact with ribosome biogenesis/protein synthesis machinery with an emphasis on their respective functions during organism development.