Design Principles for Riboswitch Function

作者: Chase L. Beisel , Christina D. Smolke

DOI: 10.1371/JOURNAL.PCBI.1000363

关键词:

摘要: Scientific and technological advances that enable the tuning of integrated regulatory components to match network system requirements are critical reliably control function biological systems. RNA provides a promising building block for construction tunable based on its rich capacity our current understanding sequence–function relationship. One prominent example RNA-based is riboswitches, genetic elements mediate ligand gene expression through diverse mechanisms. While characterization natural synthetic riboswitches has revealed riboswitch can be modulated sequence alteration, no quantitative frameworks exist investigate or guide tuning. Here, we combined mathematical modeling experimental approaches relationship between performance. Model results demonstrated competition reversible irreversible rate constants dictates performance different We also found practical restrictions, such as an upper limit concentration, significantly alter performance, necessitating alternative strategies. Previous data well experiments conducted in this work support model predictions. From results, developed set general design principles riboswitches. Our provide foundation from which how tuned meet systems-level demands.

参考文章(59)
J R Williamson, P P Zarrinkar, J Wang, Slow folding kinetics of RNase P RNA. RNA. ,vol. 2, pp. 564- 573 ,(1996)
Daniel J Klein, Adrian R Ferré-D'Amaré, Structural basis of glmS ribozyme activation by glucosamine-6-phosphate Science. ,vol. 313, pp. 1752- 1756 ,(2006) , 10.1126/SCIENCE.1129666
Travis S Bayer, Christina D Smolke, Programmable ligand-controlled riboregulators of eukaryotic gene expression Nature Biotechnology. ,vol. 23, pp. 337- 343 ,(2005) , 10.1038/NBT1069
Beatrix Suess, Julia E. Weigand, Engineered riboswitches: overview, problems and trends. RNA Biology. ,vol. 5, pp. 24- 29 ,(2008) , 10.4161/RNA.5.1.5955
Y. Yokobayashi, R. Weiss, F. H. Arnold, Directed evolution of a genetic circuit Proceedings of the National Academy of Sciences of the United States of America. ,vol. 99, pp. 16587- 16591 ,(2002) , 10.1073/PNAS.252535999
W. J. Greenleaf, K. L. Frieda, D. A. N. Foster, M. T. Woodside, S. M. Block, Direct Observation of Hierarchical Folding in Single Riboswitch Aptamers Science. ,vol. 319, pp. 630- 633 ,(2008) , 10.1126/SCIENCE.1151298
Xiangyang Zhang, Hans Bremer, None, Control of the Escherichia coli rrnB P1 promoter strength by ppGpp Journal of Biological Chemistry. ,vol. 270, pp. 11181- 11189 ,(1995) , 10.1074/JBC.270.19.11181
Tao Pan, Tobin Sosnick, RNA FOLDING DURING TRANSCRIPTION Annual Review of Biophysics and Biomolecular Structure. ,vol. 35, pp. 161- 175 ,(2006) , 10.1146/ANNUREV.BIOPHYS.35.040405.102053
Scott E. Osborne, Andrew D. Ellington, Nucleic Acid Selection and the Challenge of Combinatorial Chemistry Chemical Reviews. ,vol. 97, pp. 349- 370 ,(1997) , 10.1021/CR960009C
Sean A. Lynch, Shawn K. Desai, Hari Krishna Sajja, Justin P. Gallivan, A high-throughput screen for synthetic riboswitches reveals mechanistic insights into their function. Chemistry & Biology. ,vol. 14, pp. 173- 184 ,(2007) , 10.1016/J.CHEMBIOL.2006.12.008