Rapid responses of ribosomal RNA synthesis to nutrient shifts

Patrick F. Suthers, Richard L. Gourse, John Yin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

A major challenge in systems biology is to integrate our mechanistic understanding of gene regulation to predict quantitatively how cells will respond to environmental changes. Living cells respond rapidly to the availability of nutrients in part by altering production of ribosomal RNA (rRNA), a limiting component in the biosynthesis of ribosomes. Studies of rRNA transcription by the RNA polymerase of Escherichia coli have identified regulatory roles for guanosine tetraphosphate (ppGpp), the initiating nucleotide, and the protein DksA. To what extent findings from in vitro studies can be used to quantitatively predict in vivo responses to changing nutrient environments is unknown. We developed a mechanistic mathematical model for rRNA transcriptional responses to such changes. Our model accounts for binding of RNAP to its rRNA promoter to form a closed complex, isomerization from a closed complex to an open complex, reversible incorporation of the initiating NTP (iNTP), transcript elongation, and clearance of the promoter. Further, the model incorporates interactions between ppGpp and DksA with transcription intermediates, and it includes an empirical correction to account for salt effects. The model biophysical parameters were determined using 33 single- and multi-round transcription experiments spanning 487 in vitro measurements. By incorporating in vivo measurements of ppGpp and ATP, the model correctly predicted rRNA production rates for cellular responses to nutrient upshifts, downshifts, and outgrowth into fresh medium. Inclusion of DksA was essential in all three cases. Our work provides a foundation for using data-driven computational models to predict the kinetics of in vivo transcriptional responses.

Original languageEnglish (US)
Pages (from-to)1230-1245
Number of pages16
JournalBiotechnology and bioengineering
Volume97
Issue number5
DOIs
StatePublished - Aug 1 2007

Fingerprint

Ribosomal RNA
Nutrients
Food
Transcription
Guanosine Tetraphosphate
Systems Biology
Ribosomes
Adenosinetriphosphate
Biosynthesis
Nucleotides
Isomerization
Theoretical Models
Gene expression
Salts
Adenosine Triphosphate
Escherichia coli
Elongation
Cells
Availability
Mathematical models

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Suthers, Patrick F. ; Gourse, Richard L. ; Yin, John. / Rapid responses of ribosomal RNA synthesis to nutrient shifts. In: Biotechnology and bioengineering. 2007 ; Vol. 97, No. 5. pp. 1230-1245.
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Rapid responses of ribosomal RNA synthesis to nutrient shifts. / Suthers, Patrick F.; Gourse, Richard L.; Yin, John.

In: Biotechnology and bioengineering, Vol. 97, No. 5, 01.08.2007, p. 1230-1245.

Research output: Contribution to journalArticle

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