Toward a Whole-Cell Model of Ribosome Biogenesis: Kinetic Modeling of SSU Assembly

Tyler M. Earnest, Jonathan Lai, Ke Chen, Michael J. Hallock, James R. Williamson, Zaida Luthey-Schulten

Research output: Contribution to journalArticlepeer-review


Central to all life is the assembly of the ribosome: a coordinated process involving the hierarchical association of ribosomal proteins to the RNAs forming the small and large ribosomal subunits. The process is further complicated by effects arising from the intracellular heterogeneous environment and the location of ribosomal operons within the cell. We provide a simplified model of ribosome biogenesis in slow-growing Escherichia coli. Kinetic models of in vitro small-subunit reconstitution at the level of individual protein/ribosomal RNA interactions are developed for two temperature regimes. The model at low temperatures predicts the existence of a novel 5′→3′→central assembly pathway, which we investigate further using molecular dynamics. The higherature assembly network is incorporated into a model of in vivo ribosome biogenesis in slow-growing E. coli. The model, described in terms of reaction-diffusion master equations, contains 1336 reactions and 251 species that dynamically couple transcription and translation to ribosome assembly. We use the Lattice Microbes software package to simulate the stochastic production of mRNA, proteins, and ribosome intermediates over a full cell cycle of 120 min. The whole-cell model captures the correct growth rate of ribosomes, predicts the localization of early assembly intermediates to the nucleoid region, and reproduces the known assembly timescales for the small subunit with no modifications made to the embedded in vitro assembly network.

Original languageEnglish (US)
Pages (from-to)1117-1135
Number of pages19
JournalBiophysical journal
Issue number6
StatePublished - Sep 19 2015

ASJC Scopus subject areas

  • Biophysics


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