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

Biophysical Journal
Tyler M EarnestZaida Luthey-Schulten

Abstract

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 high-temperature 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 ...Continue Reading

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Citations

Dec 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Joseph R PetersonZaida A Luthey-Schulten
Sep 30, 2016·Journal of the Royal Society, Interface·Zhipeng WangPeter G Wolynes
Mar 16, 2017·The Journal of Physical Chemistry. B·Tyler M EarnestZaida Luthey-Schulten
Feb 10, 2018·Reports on Progress in Physics·Tyler M EarnestZaida Luthey-Schulten
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