CORDIS
EU research results

CORDIS

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

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

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.
Leaflet | Map data © OpenStreetMap contributors, Credit: EC-GISCO, © EuroGeographics for the administrative boundaries

Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

Address

Rue Michel Ange 3
75794 Paris

France

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 2 499 761

Beneficiaries (1)

Sort alphabetically

Sort by EU Contribution

Expand all

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 2 499 761

Project information

Grant agreement ID: 670301

Status

Ongoing project

  • Start date

    1 November 2015

  • End date

    31 October 2020

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 2 499 761

  • EU contribution

    € 2 499 761

Hosted by:

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France