The homeostatic regulation of ribosome biogenesis

The continued integrity of biological systems depends on a balance between interdependent elements at the molecular, cellular, and organismal levels. This is particularly true for the generation of ribosomes, which influence almost every aspect of cell and organismal biology. Ribosome biogenesis (RiBi) is an energetically demanding process that involves all three RNA polymerases, numerous RNA processing factors, chaperones, and the coordinated expression of 79-80 ribosomal proteins (r-proteins). Work over the last several decades has revealed that the dynamic regulation of ribosome production represents a major mechanism by which cells maintain homeostasis in response to changing environmental conditions and acute stress. More recent studies suggest that cells and tissues within multicellular organisms exhibit dramatically different levels of ribosome production and protein synthesis, marked by the differential expression of RiBi factors. Thus, distinct bottlenecks in the RiBi process, downstream of rRNA transcription, may exist within different cell populations of multicellular organisms during development and in adulthood. This review will focus on our current understanding of the mechanisms that link the complex molecular process of ribosome biogenesis with cellular and organismal physiology. We will discuss diverse topics including how different steps in the RiBi process are coordinated with one another, how MYC and mTOR impact RiBi, and how RiBi levels change between stem cells and their differentiated progeny. In turn, we will also review how regulated changes in ribosome production itself can feedback to influence cell fate and function.