Toward a Whole-Cell Model of Ribosome Biogenesis: Kinetic Modeling of SSU Assembly.
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 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.
Center for the Physics of Living Cells, University of Illinois, Urbana, Illinois; Department of Physics, University of Illinois, Urbana, Illinois.
Emmy E
EE
Earnest
Department of Chemistry, University of Illinois, Urbana, Illinois.
Jonathan
J
Lai
Department of Chemistry, University of Illinois, Urbana, Illinois; Department of Bioengineering, University of California, San Diego, La Jolla, California.
Ke
K
Chen
School of Chemical Sciences, University of Illinois, Urbana, Illinois.
Michael J
MJ
Hallock
Department of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, California; Department of Chemistry, Scripps Research Institute, La Jolla, California; Skaggs Institute for Chemical Biology, Scripps Research Institute, La Jolla, California.
James R
JR
Williamson
Center for the Physics of Living Cells, University of Illinois, Urbana, Illinois; Department of Physics, University of Illinois, Urbana, Illinois; Department of Chemistry, University of Illinois, Urbana, Illinois. Electronic address: zan@illinois.edu.
Zaida
Z
Luthey-Schulten
D003080:Cold Temperature; D003198:Computer Simulation; D004058:Diffusion; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D006358:Hot Temperature; D007700:Kinetics; D008954:Models, Biological; D001678:Organelle Biogenesis; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D012984:Software; D013269:Stochastic Processes
D029968:Escherichia coli Proteins; D012333:RNA, Messenger