The translational machinery is an optimized molecular network that affects cellular homoeostasis and disease

Abstract

Translation involves interactions between mRNAs, ribosomes, tRNAs and a host of translation factors. Emerging evidence on the eukaryotic translational machinery indicates that these factors are organized in a highly optimized network, in which the levels of the different factors are finely matched to each other. This optimal factor network is essential for producing proteomes that result in optimal fitness, and perturbations to the optimal network that significantly affect translational activity therefore result in non-optimal proteomes, fitness losses and disease. On the other hand, experimental evidence indicates that translation and cell growth are relatively robust to perturbations, and viability can be maintained even upon significant damage to individual translation factors. How the eukaryotic translational machinery is optimized, and how it can maintain optimization in the face of changing internal parameters, are open questions relevant to the interaction between translation and cellular disease states.

Control and regulation of mRNA translation

“…In this issue, Kazana and von der Haar [21] explore the concept that an ideal component arrangement of the gene expression machinery into a finely tuned network elicits optimal performance of mRNA translation. They present a persuasive argument for the apparent robustness of the eukaryotic translational machinery to perturbation in engineering terms, while highlighting how, in contradiction to this, the fine balance of the network is susceptible to both internal and external influences and give examples of resulting disease states.…”