Synthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites

 

Synthetic posttranscriptional regulation of gene expression is important when it comes to 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. This article introduces a broadly applicable strategy for 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. This strategy reduces ‘leakiness’ to improve overall expression dynamic range, and can be implemented without sacrificing modularity and cross-organism functionality.This articles shows this approach across two unrelated organisms, the model yeast S. cerevisiae and the human malarial parasite, P. falciparum. In the latter organism, where few tools are available for studying gene function, technology can be used to stringently classify genes essential for parasite survival. TetR fusion proteins conditionally regulate translation. The TetR protein module is regulated by tetracycline analogues as the foundational framework for this study. This module has been used in a uni-dimensional context to control translation in the model organism, S. cerevisiae and the unrelated human malarial pathogen, P. falciparum. Second, the Dhh1p homologue from the related rodent malarial parasite, P. berghei, has been implicated in translational regulation. Deleting this protein disregulates the stability of many transcripts that are normally repressed during asexual-stage development in blood and derepressed during sexual-stage development in the mosquito vector. The essential function of P. falciparum  membrane protein, PfATP4, which is a new antimalarial drug target/resistance mechanism. This P-type ATPase protein has been proposed as the putative target of a new, potent and clinically promising antimalarial drug class, the spiroindolones. However, the available evidence does not demonstrate that loss of PfATP4 function should, in fact, impair parasite survival. The availability of this information gives great significance indicating that many diverse chemical scaffolds converge on PfATP4 as a common direct or indirect mechanism of parasite sensitivity and/or resistance to these compounds.

This article stood out to me because it had to deal wit Malaria. It talks about gene expression, transcription, and translation. This article was very informative and had a lot of new information in regards to malaria. If the correct drugs are used, people who are infected with malaria can be cured. All the malaria parasites can be cleared from their body with the right medicine. However, the disease can continue if it is not treated or if it is treated with the wrong drug. Some drugs are not effective because the parasite is resistant to them. This article discusses how P-type ATPase protein has been proposed as the putative target of a new, potent and clinically promising antimalarial drug. This was an overall great article.

Ganesan, S. M. et al. Synthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites. Nat. Commun. 7:10727 doi: 10.1038/ncomms10727 (2016).