Rapid responses of ribosomal RNA synthesis to nutrient shifts.
Rapid responses of ribosomal RNA synthesis to nutrient shifts.
复制标题
核糖体 RNA 合成对营养变化的快速反应。
DOI：
10.1002/bit.21318
复制
发表时间：
2007
影响因子：
3.8
通讯作者：
Yin,John
中科院分区：
文献类型：
--
作者：
Suthers,PatrickF;Gourse,RichardL;Yin,John
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 ofEscherichia colihave 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. Biotechnol. Bioeng. 2007; 97: 1230–1245. © 2007 Wiley Periodicals, Inc.
