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PlasmoSilencing SIGNED

Exoribonuclease-mediated degradation of nascent RNA in Malaria Parasites: A Novel Mechanism in Virulence Gene Silencing

Total Cost €

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EC-Contrib. €

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Partnership

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 PlasmoSilencing project word cloud

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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
address: RUE MICHEL ANGE 3
city: PARIS
postcode: 75794
website: www.cnrs.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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.

# participants  country  role  EC contrib. [€] 
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
List of publications.
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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