Controlling gene expression in malaria parasites with synthetic RNA-protein modules

Controlling gene expression in malaria parasites with synthetic RNA-protein modules

Current strategies for regulatory control of gene expression are orthogonal to the host organism mechanisms. Here the authors demonstrate an RNA aptamer controlled system integrated into native regulatory pathways in the parasite Plasmodium falciparum.

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.

Researchers 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.

They demonstrate that this strategy reduces ‘leakiness’ to improve overall expression dynamic range, and can be implemented without sacrificing modularity and cross-organism functionality.

Authors illustrate this in Saccharomyces cerevisae and the non-model human malarial parasite,Plasmodium falciparum. Given the limited functional genetics toolkit available for P. falciparum, they establish the utility of this strategy for defining essential genes.

http://www.nature.com/ncomms/2016/160301/ncomms10727/full/ncomms10727.html

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