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Import of human miRNA-RISC complex into Plasmodium falciparum and regulation of the parasite gene expression

  • Vishal Dandewad
  • Arya Vindu
  • Jomon Joseph
  • Vasudevan SeshadriEmail author
Brief communication
  • 12 Downloads

Abstract

During its life cycle, the malarial parasite Plasmodium goes through different asexual stages in human blood, and asexual and sexual stage in mosquito. Expression of stage-specific proteins is important for successful completion of its life cycle and requires tight gene regulation. In case of Plasmodium, due to relative paucity of the transcription factors, it is postulated that post-transcriptional regulation plays an important role in stage-specific gene expression. Although miRNA-mediated gene regulation has been well-established to function in post-transcriptional regulation in many eukaryotes, existence of such a phenomenon or the presence of miRNA-associated factors in Plasmodium remains unclear. A number of miRNAs are shown to be imported into Plasmodium falciparum from erythrocytes and role of these miRNAs is not understood. Here we show that human Argonaute 2 (hAgo2) a component of the miRISC complex is imported by P. falciparum. In the parasite hAgo2 exists as in a complex with specific human miRNAs like let-7a and miR15a which can potentially target the Plasmodium genes Rad54 and Lipid/sterol:H+ symporter respectively. We show that hAgo2 associates with Rad54, Lipid/sterol:H+ symporter and other P. falciparum transcripts. These results highlight the existence of a mechanism by which malarial parasite imports hAgo2-miRNA complex from the host cells to regulate its gene expression.

Keywords

Argonaute miRNA Plasmodium falciparum 

Notes

Acknowledgements

We thank Dr. Swati Patankar for the gift of 3D7 culture. This work has been funded by the grant to VS from NCCS (intramural) and Department of Science and Technology, Government of India (EMR/2014/001093). VD was supported by fellowship from Department of Biotechnology, India and AV was supported fellowship from Council for Scientific and Industrial Research, India.

Supplementary material

12038_2019_9870_MOESM1_ESM.pdf (637 kb)
Supplementary material 1 (PDF 637 kb)

References

  1. Azzouzi I, Moest H, Wollscheid B, Schmugge M, Eekels JJM and Speer O 2015 Deep sequencing and proteomic analysis of the microRNA-induced silencing complex in human red blood cells. Exp. Hematol. 43 382–392CrossRefGoogle Scholar
  2. Baum J, Papenfuss AT, Mair GR, Janse CJ, Vlachou D, Waters AP, Cowman AF, Crabb BS, De Koning-Ward TF and Koning-ward TF De 2009 Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res. 37 3788–3798CrossRefGoogle Scholar
  3. Chakrabarti K, Pearson M, Grate L, Sterne-weiler T, Deans J, Donohue JP and Jr Ares M 2007 Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis. RNA 13 1923–1939CrossRefGoogle Scholar
  4. Chen S, Wang Y, Telen MJ and Chi J 2008 The genomic analysis of erythrocyte microRNA expression in sickle cell diseases. PLoS One 3 e2360 1–13Google Scholar
  5. Coulson RMR, Hall N and Ouzounis CA 2004 Comparative genomics of transcriptional control in the human malaria parasite Plasmodium falciparum. Genome Res. 14 1548–1554CrossRefGoogle Scholar
  6. Dechering KJ, Cuelenaere K, Konings RNH and Leunissen JAM 1998 Distinct frequency-distributions of homopolymeric DNA tracts in different genomes. Nucleic Acids Res. 26 4056–4062CrossRefGoogle Scholar
  7. Didiano D and Hobert O 2008 Molecular architecture of a miRNA-regulated 3′UTR. RNA 14 1297–1317CrossRefGoogle Scholar
  8. Filipowicz W, Bhattacharyya SN and Sonenberg N 2008 Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat. Rev. Genet. 9 102–114CrossRefGoogle Scholar
  9. Foth BJ, Zhang N, Mok S, Preiser PR and Bozdech Z 2008 Quantitative protein expression profiling reveals extensive post-transcriptional regulation and post-translational modifications in schizont-stage malaria parasites. Genome Biol. 9 R177.1-18CrossRefGoogle Scholar
  10. Hall N, Karras M, Raine JD, Carlton JM, Kooij TWA, Berriman M, Florens L, Janssen CS, Pain A, Christophides GK, et al. 2005 A comprehensive survey of the plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 307 82–87CrossRefGoogle Scholar
  11. Kannan M and Atreya C 2010 Differential profiling of human red blood cells during storage for 52 selected microRNAs. Transfusion 50 1581–1588CrossRefGoogle Scholar
  12. Khraiwesh B, Arif MA, Seumel GI, Ossowski S, Weigel D, Reski R and Frank W 2010 Transcriptional control of gene expression by MicroRNAs. Cell 140 111–122CrossRefGoogle Scholar
  13. Koncarevic S, Rohrbach P, Deponte M, Krohne G, Helena J, Yates J, Rahlfs S and Becker K 2009 The malarial parasite Plasmodium falciparum imports the human protein peroxiredoxin 2 for peroxide detoxification. Proc. Natl. Acad. Sci. USA 106 13323–13328CrossRefGoogle Scholar
  14. Kooij TWA and Matuschewski K 2007 Triggers and tricks of Plasmodium sexual development. Curr. Opin. Microbiol. 10 547–553CrossRefGoogle Scholar
  15. Lacsina JR, LaMonte G, Nicchitta C V and Chi J-T 2011 Polysome profiling of the malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 179 42–46CrossRefGoogle Scholar
  16. Lamonte G, Philip N, Reardon J, Lacsina JR, Majoros W, Chapman L, Thornburg CD, Telen MJ, Ohler U, Nicchitta C V, et al. 2012 Translocation of sickle cell erythrocyte MicroRNAs into Plasmodium falciparum inhibits parasite translation and contributes to malaria resistance. Cell Host Microbe 12 187–199CrossRefGoogle Scholar
  17. Mantel PY, Hoang AN, Goldowitz I, Potashnikova D, Hamza B, Vorobjev I, Ghiran I, Toner M, Irimia D, Ivanov AR, et al. 2013 Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 13 521–534CrossRefGoogle Scholar
  18. Mantel PY, Hjelmqvist D, Walch M, Kharoubi-Hess S, Nilsson S, Ravel D, Ribeiro M, Grüring C, Ma S, Padmanabhan P, et al. 2016 Infected erythrocyte-derived extracellular vesicles alter vascular function via regulatory Ago2-miRNA complexes in malaria. Nat. Commun. 7 12727CrossRefGoogle Scholar
  19. Ofir-Birin Y, Heidenreich M and Regev-Rudzki N 2017 Pathogen-derived extracellular vesicles coordinate social behaviour and host manipulation. Semin. Cell Dev. Biol. 67 83–90CrossRefGoogle Scholar
  20. Radfar A, Méndez D, Moneriz C, Linares M, Marín-garcía P, Puyet A, Diez A and Bautista JM 2009 Synchronous culture of Plasmodium falciparum at high parasitemia levels. Nat. Protoc. 4 1899–1915CrossRefGoogle Scholar
  21. Regev-Rudzki N, Wilson DW, Carvalho TG, Sisquella X, Coleman BM, Rug M, Bursac D, Angrisano F, Gee M, Hill AF, et al. 2013 Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 153 1120–1133CrossRefGoogle Scholar
  22. Saliba KJ, Folb PI and Smith PJ 1998 Role for the Plasmodium falciparum digestive vacuole in chloroquine resistance. Biochem. Pharmacol. 56 313–320CrossRefGoogle Scholar
  23. Saraiya AA and Wang CC 2008 snoRNA a novel precursor of microRNA in Giardia lamblia. PLoS Pathog. 4 e1000224 1-10Google Scholar
  24. Trager W and Jensen JB 1976 Human malaria parasites in continuous culture. Science 193 673–675CrossRefGoogle Scholar
  25. Wang Z, Xi J, Hao X, Deng W, Liu J, Wei C, Gao Y, Zhang L and Wang H 2017 Red blood cells release microparticles containing human argonaute 2 and miRNAs to target genes of Plasmodium falciparum. Emerg. Microbes Infect. 6 e75 1-11Google Scholar
  26. Xue X, Zhang Q, Huang Y, Feng L and Pan W 2008 No miRNA were found in Plasmodium and the ones identified in erythrocytes could not be correlated with infection. Malar. J. 6 1–6Google Scholar
  27. Zhou X, Duan ÆX, Qian ÆJ and, Microrna K 2009 Abundant conserved microRNA target sites in the 5′-untranslated region and coding sequence. Genetica 137 159–164CrossRefGoogle Scholar

Copyright information

© Indian Academy of Sciences 2019

Authors and Affiliations

  1. 1.National Centre for Cell SciencePuneIndia
  2. 2.Department of BiotechnologySavitribai Phule Pune UniversityPuneIndia

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