RNA polymerase III is involved in regulating Plasmodium falciparum virulence.

Autor: Diffendall G; Institut Pasteur, Universite Paris Cité, Paris, France.; Institut Pasteur, Sorbonne Université Ecole doctorale Complexité du Vivant, Paris, France., Claes A; Institut Pasteur, Universite Paris Cité, Paris, France., Barcons-Simon A; Institut Pasteur, Universite Paris Cité, Paris, France.; Institut Pasteur, Sorbonne Université Ecole doctorale Complexité du Vivant, Paris, France.; Institut Pasteur, Biomedical Center, Division of Physiological Chemistry, Faculty of Medicine, Ludwig-Maximilians-Universität München, Munich, Germany., Nyarko P; Institut Pasteur, Laboratory of Pathogen-Host Interaction (LPHI), CNRS, University of Montpellier, Montpellier, France., Dingli F; Institut Pasteur, Institut Curie, PSL Research University, Centre de Recherche, CurieCoreTech Mass Spectrometry Proteomics, Paris, France., Santos MM; Institut Pasteur, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal., Loew D; Institut Pasteur, Institut Curie, PSL Research University, Centre de Recherche, CurieCoreTech Mass Spectrometry Proteomics, Paris, France., Claessens A; Institut Pasteur, Laboratory of Pathogen-Host Interaction (LPHI), CNRS, University of Montpellier, Montpellier, France.; Institut Pasteur, LPHI, MIVEGEC, CNRS, INSERM, University of Montpellier, Montpellier, France., Scherf A; Institut Pasteur, Universite Paris Cité, Paris, France.
Jazyk: angličtina
Zdroj: ELife [Elife] 2024 Jun 26; Vol. 13. Date of Electronic Publication: 2024 Jun 26.
DOI: 10.7554/eLife.95879
Abstrakt: While often undetected and untreated, persistent seasonal asymptomatic malaria infections remain a global public health problem. Despite the presence of parasites in the peripheral blood, no symptoms develop. Disease severity is correlated with the levels of infected red blood cells (iRBCs) adhering within blood vessels. Changes in iRBC adhesion capacity have been linked to seasonal asymptomatic malaria infections, however how this is occurring is still unknown. Here, we present evidence that RNA polymerase III (RNA Pol III) transcription in Plasmodium falciparum is downregulated in field isolates obtained from asymptomatic individuals during the dry season. Through experiments with in vitro cultured parasites, we have uncovered an RNA Pol III-dependent mechanism that controls pathogen proliferation and expression of a major virulence factor in response to external stimuli. Our findings establish a connection between P. falciparum cytoadhesion and a non-coding RNA family transcribed by Pol III. Additionally, we have identified P. falciparum Maf1 as a pivotal regulator of Pol III transcription, both for maintaining cellular homeostasis and for responding adaptively to external signals. These results introduce a novel perspective that contributes to our understanding of P. falciparum virulence. Furthermore, they establish a connection between this regulatory process and the occurrence of seasonal asymptomatic malaria infections.
Competing Interests: GD, AC, AB, PN, FD, MS, DL, AC, AS No competing interests declared
(© 2024, Diffendall et al.)
Databáze: MEDLINE