Context-Specific Regulation of Coupled Transcription-Translation Modules Predicts Pervasive Ribosome Specialization

Abstract

The ribosome is a defining structure of all cellular organisms and represents the uniquely biological process of translation. Although ribosomes are typically represented as molecular assembly lines that constitutively perform coded protein synthesis, translation is a system property that emerges from interactions among diverse types of cellular components, including different classes of RNAs, proteins, and amino acids. The prevailing view that all ribosomes within a cell are structurally identical and functionally equivalent was challenged long ago, and is becoming increasingly less tenable with modern experimental tools. Through analysis of environmental and gene regulatory influence networks of H. salinarum, E. coli, and S. cerevisiae, we have discovered a generalized pattern of extensive, environment-specific modularity and heterogeneity in translational subsystems across these representative organisms from each of the three domains of life (Archaea, Bacteria and Eukarya). Systems analysis of H. salinarum growth-associated changes in total mRNA abundance (RNA-seq), ribosome associated transcripts (ribosome profiling), and protein abundance (SWATH-MS proteomics) further support the hypothesis that ribosomes are less of a singular entity, and more of a mosaic patchwork. These data provide evidence that variability in translational subsystems might confer intrinsic regulation of protein synthesis by selectively translating subsets of the transcriptome. We discuss the implication of linked translation-transcription modules as a minimal set of molecules for steering physiological state transitions, as well as acting as a fundamental constraint on biological evolution.