PlasmoSilencing SIGNED
Exoribonuclease-mediated degradation of nascent RNA in Malaria Parasites: A Novel Mechanism in Virulence Gene Silencing
Total Cost €
0EC-Contrib. €
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Project "PlasmoSilencing" data sheet
The following table provides information about the project.
| Coordinator |
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Organization address contact info |
| Coordinator Country | France [FR] |
| Project website | https://research.pasteur.fr/en/team/biology-of-host-parasite-interactions/ |
| Total cost | 2˙499˙761 € |
| EC max contribution | 2˙499˙761 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-ADG |
| Funding Scheme | ERC-ADG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-11-01 to 2020-10-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS | FR (PARIS) | coordinator | 2˙499˙761.00 |
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Project objective
Background: The human protozoan malaria parasite P. falciparum causes approximately 200 million infections and 0.7 million deaths (mainly children) per year. In the well-studied asexual blood stages, cyclic monocistronic gene activation occurs at the transcriptional level; however, relatively few transcription factors have been identified, thus other types of regulatory processes that contribute to this coordinated gene expression are believed to exist. Through the study of molecular process of monoallelic expression of immune evasion genes in P. falciparum (project funded by a previous ERC grant to A. Scherf), we discovered an entirely new mechanism of gene silencing. We demonstrated that an exoribonuclease silences genes linked to severe malaria. A non-canonical 3’-5’exoribonuclease termed PfRNase II destroys nascent RNA made from promoter regions, leading to cryptic unstable mRNA. Parasites carrying a deficient PfRNase II produce full-length mRNA and long noncoding RNA. The molecular events and the number of genes directly controlled by this novel type of posttranscriptional gene silencing remain elusive. Aim: This proposal aims to investigate the molecular mechanisms controlling PfRNase II-dependent gene silencing using innovative strategies such as the new genome editing technique (Cas9/CRISPR) developed in my laboratory for use in P. falciparum. We will study i) the recruitment of PfRNase II to promoter regions of severe malaria related genes using protein pull-down assays and ii) the genome occupancy of PfRNase II and two other 3’-5’ exoribonucleases to determine the total number of genes controlled by this mechanism. Impact: This project represents a major change in mainstream malaria parasite gene regulation paradigms with repercussions for other organisms. The proposed research will both open new avenues in molecular process that control severe malaria and appeal to young researchers to join this rather ‘untouched’ topic.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2016 |
Shruthi Sridhar Vembar, Matthew Seetin, Christine Lambert, Maria Nattestad, Michael C. Schatz, Primo Baybayan, Artur Scherf, Melissa Laird Smith Complete telomere-to-telomere de novo assembly of the Plasmodium falciparum genome through long-read (>11 kb), single molecule, real-time sequencing published pages: 339-351, ISSN: 1340-2838, DOI: 10.1093/dnares/dsw022 |
DNA Research 23/4 | 2019-07-05 |
| 2017 |
Jessica M. Bryant, Clément Regnault, Christine Scheidig-Benatar, Sebastian Baumgarten, Julien Guizetti, Artur Scherf CRISPR/Cas9 Genome Editing Reveals That the Intron Is Not Essential for var2csa Gene Activation or Silencing in Plasmodium falciparum published pages: , ISSN: 2150-7511, DOI: 10.1128/mBio.00729-17 |
mBio 8/4 | 2019-07-05 |
| 2018 |
Jessica M. Bryant, Sebastian Baumgarten, Audrey Lorthiois, Christine Scheidig-Benatar, Aurélie Claës, Artur Scherf De Novo Genome Assembly of a Plasmodium falciparum NF54 Clone Using Single-Molecule Real-Time Sequencing published pages: , ISSN: 2169-8287, DOI: 10.1128/genomeA.01479-17 |
Genome Announcements 6/5 | 2019-07-05 |
| 2018 |
Gigliola Zanghì, Shruthi S. Vembar, Sebastian Baumgarten, Shuai Ding, Julien Guizetti, Jessica M. Bryant, Denise Mattei, Anja T.R. Jensen, Laurent Rénia, Yun Shan Goh, Robert Sauerwein, Cornelus C. Hermsen, Jean-François Franetich, Mallaury Bordessoulles, Olivier Silvie, Valérie Soulard, Olivier Scatton, Patty Chen, Salah Mecheri, Dominique Mazier, Artur Scherf A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection published pages: 2951-2963, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.02.075 |
Cell Reports 22/11 | 2019-07-05 |
| 2017 |
Rafael M. Martins, Cameron R. Macpherson, Aurélie Claes, Christine Scheidig-Benatar, Hiroshi Sakamoto, Xue Yan Yam, Peter Preiser, Suchi Goel, Mats Wahlgren, Odile Sismeiro, Jean-Yves Coppée, Artur Scherf An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-12578-y |
Scientific Reports 7/1 | 2019-07-05 |
| 2017 |
Fabien Sindikubwabo, Shuai Ding, Tahir Hussain, Philippe Ortet, Mohamed Barakat, Sebastian Baumgarten, Dominique Cannella, Andrés Palencia, Alexandre Bougdour, Lucid Belmudes, Yohann Couté, Isabelle Tardieux, Cyrille Y Botté, Artur Scherf, Mohamed-ali Hakimi Modifications at K31 on the lateral surface of histone H4 contribute to genome structure and expression in apicomplexan parasites published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.29391 |
eLife 6 | 2019-07-05 |
| 2016 |
Julien Guizetti, Anna Barcons-Simon, Artur Scherf Trans-acting GC-rich non-coding RNA at var expression site modulates gene counting in malaria parasite published pages: gkw664, ISSN: 0305-1048, DOI: 10.1093/nar/gkw664 |
Nucleic Acids Research | 2019-07-05 |
| 2016 |
Shruthi Sridhar Vembar, Dorothea Droll, Artur Scherf Translational regulation in blood stages of the malaria parasite Plasmodium spp. : systems-wide studies pave the way published pages: 772-792, ISSN: 1757-7004, DOI: 10.1002/wrna.1365 |
Wiley Interdisciplinary Reviews: RNA 7/6 | 2019-07-05 |
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