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

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  • Suresh M. Ganesan

    (Massachusetts Institute of Technology)

  • Alejandra Falla

    (Massachusetts Institute of Technology)

  • Stephen J. Goldfless

    (Massachusetts Institute of Technology
    Present address: AbVitro Inc., 27 Drydock Avenue, Boston, Massachusetts 02210, USA)

  • Armiyaw S. Nasamu

    (Massachusetts Institute of Technology)

  • Jacquin C. Niles

    (Massachusetts Institute of Technology)

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.

Suggested Citation

  • Suresh M. Ganesan & Alejandra Falla & Stephen J. Goldfless & Armiyaw S. Nasamu & Jacquin C. Niles, 2016. "Synthetic RNA–protein modules integrated with native translation mechanisms to control gene expression in malaria parasites," Nature Communications, Nature, vol. 7(1), pages 1-10, April.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10727
    DOI: 10.1038/ncomms10727
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    Cited by:

    1. Hui Min & Xiaoying Liang & Chengqi Wang & Junling Qin & Rachasak Boonhok & Azhar Muneer & Awtum M. Brashear & Xiaolian Li & Allen M. Minns & Swamy Rakesh Adapa & Rays H. Y. Jiang & Gang Ning & Yaming , 2024. "The DEAD-box RNA helicase PfDOZI imposes opposing actions on RNA metabolism in Plasmodium falciparum," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Deyun Qiu & Jinxin V. Pei & James E. O. Rosling & Vandana Thathy & Dongdi Li & Yi Xue & John D. Tanner & Jocelyn Sietsma Penington & Yi Tong Vincent Aw & Jessica Yi Han Aw & Guoyue Xu & Abhai K. Tripa, 2022. "A G358S mutation in the Plasmodium falciparum Na+ pump PfATP4 confers clinically-relevant resistance to cipargamin," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Marvin Chew & Weijian Ye & Radoslaw Igor Omelianczyk & Charisse Flerida Pasaje & Regina Hoo & Qingfeng Chen & Jacquin C. Niles & Jianzhu Chen & Peter Preiser, 2022. "Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Laura E. Vries & Patrick A. M. Jansen & Catalina Barcelo & Justin Munro & Julie M. J. Verhoef & Charisse Flerida A. Pasaje & Kelly Rubiano & Josefine Striepen & Nada Abla & Luuk Berning & Judith M. Bo, 2022. "Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Thomas Hollin & Steven Abel & Alejandra Falla & Charisse Flerida A. Pasaje & Anil Bhatia & Manhoi Hur & Jay S. Kirkwood & Anita Saraf & Jacques Prudhomme & Amancio De Souza & Laurence Florens & Jacqui, 2022. "Functional genomics of RAP proteins and their role in mitoribosome regulation in Plasmodium falciparum," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    6. Stanley C. Xie & Yinuo Wang & Craig J. Morton & Riley D. Metcalfe & Con Dogovski & Charisse Flerida A. Pasaje & Elyse Dunn & Madeline R. Luth & Krittikorn Kumpornsin & Eva S. Istvan & Joon Sung Park &, 2024. "Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    7. Alexander A. Morano & Rachel M. Rudlaff & Jeffrey D. Dvorin, 2023. "A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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