Synthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites
Name
Ganesan-2016-Synthetic RNA.pdf
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Author(s)
Ganesan, Suresh Maddur
Falla Castillo, Diana Alejandra
Goldfless, Stephen Jacob
Nasamu, Armiyaw Sebastian
Niles, Jacquin C.
Date Issued
March 2016
Journal
Nature Communications
Publisher
Springer Nature
Citation
Ganesan, Suresh M., Alejandra Falla, Stephen J. Goldfless, Armiyaw S. Nasamu, and Jacquin C. Niles. "Synthetic RNA-protein modules integrated with native translation mechanisms to control gene expression in malaria parasites." Nature Communications 7, Article number: 10727 (2016), pp.1-10.
Version
Final published version
Abstract
Synthetic posttranscriptional regulation of gene expression is important for understanding fundamental biology and programming new cellular processes in synthetic biology. Previous strategies for regulating translation in eukaryotes have focused on disrupting individual steps in translation, including initiation and mRNA cleavage. In emphasizing modularity and cross-organism functionality, these systems are designed to operate orthogonally to native control mechanisms. Here we introduce a broadly applicable strategy for robustly controlling protein translation by integrating synthetic translational control via a small-molecule-regulated RNA–protein module with native mechanisms that simultaneously regulate multiple facets of cellular RNA fate. We demonstrate that this strategy reduces ‘leakiness’ to improve overall expression dynamic range, and can be implemented without sacrificing modularity and cross-organism functionality. We illustrate this in Saccharomyces cerevisae and the non-model human malarial parasite, Plasmodium falciparum. Given the limited functional genetics toolkit available for P. falciparum, we establish the utility of this strategy for defining essential genes.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1038/ncomms10727
