RNA polymerase III is involved in regulating Plasmodium falciparum virulence

• DOI: 10.7554/elife.95879.2
• Publication Date: 2024-04-11T17:25:33Z
• Authors: Gretchen Diffendall; Aurélie Claës; Anna Barcons-Simon; Prince Nyarko; Florent Dingli; Miguel Santos; Damarys Loew; Antoine Claessens; Artur Scherf
• Keywords: 0301 basic medicine; Erythrocytes; QH301-705.5; Virulence Factors; infectious disease; Science; Plasmodium falciparum; malaria; Protozoan Proteins; P. falciparum; var genes; 03 medical and health sciences; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]; Cell Adhesion; Humans; [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology; Biology (General); Malaria, Falciparum; Microbiology and Infectious Disease; Virulence; microbiology; Q; R; RNA Polymerase III; ncRNA; virulence; Gene Expression Regulation; [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases; [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN]; Medicine; [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology

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 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.