Transcriptome-wide dynamics of extensive m 6 A mRNA methylation during Plasmodium falciparum blood-stage development.

Autor: Baumgarten S; Biology of Host-Parasite Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France. sebastian.baumgarten@pasteur.fr.; CNRS, ERL 9195, Paris, France. sebastian.baumgarten@pasteur.fr.; INSERM, Unit U1201, Paris, France. sebastian.baumgarten@pasteur.fr., Bryant JM; Biology of Host-Parasite Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France.; CNRS, ERL 9195, Paris, France.; INSERM, Unit U1201, Paris, France., Sinha A; School of Biological Sciences, Nanyang Technological University Singapore, Singapore, Singapore.; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore., Reyser T; Biology of Host-Parasite Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France.; CNRS, ERL 9195, Paris, France.; INSERM, Unit U1201, Paris, France.; Laboratoire de Chimie de Coordination, Toulouse, France., Preiser PR; School of Biological Sciences, Nanyang Technological University Singapore, Singapore, Singapore.; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore., Dedon PC; Antimicrobial Resistance Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Singapore, Singapore.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA., Scherf A; Biology of Host-Parasite Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, Paris, France.; CNRS, ERL 9195, Paris, France.; INSERM, Unit U1201, Paris, France.
Jazyk: angličtina
Zdroj: Nature microbiology [Nat Microbiol] 2019 Dec; Vol. 4 (12), pp. 2246-2259. Date of Electronic Publication: 2019 Aug 05.
DOI: 10.1038/s41564-019-0521-7
Abstrakt: Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-h life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N 6 -methyladenosine (m 6 A) over the course of blood-stage development. Using mass spectrometry and m 6 A RNA sequencing, we demonstrate that m 6 A is highly developmentally regulated, exceeding m 6 A levels known in any other eukaryote. We characterize a distinct m 6 A writer complex and show that knockdown of the putative m 6 A methyltransferase, PfMT-A70, by CRISPR interference leads to increased levels of transcripts that normally contain m 6 A. In accordance, we find an inverse correlation between m 6 A methylation and mRNA stability or translational efficiency. We further identify two putative m 6 A-binding YTH proteins that are likely to be involved in the regulation of these processes across the parasite's life cycle. Our data demonstrate unique features of an extensive m 6 A mRNA methylation programme in malaria parasites and reveal its crucial role in dynamically fine-tuning the transcriptional cascade of a unicellular eukaryote.
Databáze: MEDLINE
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