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Last Updated: 29/11/2022

Resolving m6A-mediated post-transcriptional control in the human malaria parasite

Objectives

To investigate the role of this post-transcriptional modification on the parasite developmental stages by focusing on mRNA methylation of adenosines (m6A). 

Specific Objectives:

  1. Characterize m6A-binding proteins and elucidate how different m6A ‘readers’ translate this mRNA modification into distinct biological pathways (i.e. degradation, repression) during blood-stage development. 
  2. Investigate how m6A and its specific reader proteins designate mRNAs to facilitate transient quiescence in transmission stages (i.e. gametocytes and sporozoites) to ‘prime’ the transcriptome for new host/vector environments. Overall, exploring the epitranscriptome of this parasite will reveal novel principles and molecular determinants of post-transcriptional control that can be targeted to combat malaria.

Project results will unveil the determinants that translate these mRNA modifications into distinct biological pathways and pave the way towards the identification of novel targets to combat malaria.

Principal Institution

Institut Pasteur, France

Principal Investigators / Focal Persons

Sebastian Baumgarten

Rationale and Abstract

Post-transcriptional regulation in malaria parasites is key to the progression through different developmental stages of the complex life cycle within the human and mosquito host. This includes the asexual proliferation within human red blood cells that is responsible for all clinical symptoms of the disease and the preparation for the environmental changes accompanying transmission from host to vector and vice versa. Although the process that controls the destiny of mRNA are of critical importance to parasite survival and transmission, the molecular mechanisms orchestrating post-transcriptional regulation on a transcriptome-wide level remain largely unknown. We recently identified extensive methylation of adenosines (m6A) at internal mRNA positions as a new layer of post-transcriptional regulation of gene expression in Plasmodium falciparum. With m6A, the parasite dynamically modulates its transcriptome through selective mRNA degradation and/or translational repression of modified transcripts during blood-stage development. This new epitranscriptomic layer provides a previously missing link between the transcriptional program and the observed post-transcriptional events throughout P. falciparum development. 

Date

Jun 2021 — May 2026

Total Project Funding

$1.7M

Funding Details
European Research Council (ERC), Belgium

Grant agreement ID: 947819
€1.5 Million
Project Site

France

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