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Environmental inhibition of RNA Pol III reduces malaria parasite virulence (during asymptomatic infection)

ABSTRACT: During the dry season, in many African regions, persistent asymptomatic malaria cases have been linked to downregulated virulence gene expression encoded by the var gene family, resulting in low adhesion and increased circulation time of Plasmodium falciparum-infected erythrocytes 1. Several studies have investigated associations between parasite transcription and clinical severity, but the underlying process that results in lower virulence gene expression in asymptomatic malaria remains unknown. Here we report an RNA Polymerase III-dependent mechanism that in response to external stimuli, decreases var gene transcription and parasite multiplication rate. The singular expression of var gene members, while under tight epigenetic regulation by the parasite 2, is additionally controlled by a family of ncRNA, termed RUF6 3. We show that Pol III transcription of tRNAs and RUF6 is severely decreased in field isolates of asymptomatic individuals infected with P. falciparum during the dry season. We identified Maf1 as a negative effector of RUF6 ncRNA transcription and show that external stimuli depend on plasmodial Maf1 to trigger lower expression of RNA Pol III-transcribed genes. Our results uncover a TOR-independent unprecedented signaling pathway in a protozoan pathogen that is highly relevant for establishing asymptomatic subclinical parasite persistence in the dry season.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Plasmodium Falciparum

TISSUE(S): Cell Culture

DISEASE(S): Malaria

SUBMITTER: Vanessa Masson

LAB HEAD: Damarys Loew

PROVIDER: PXD040576 | Pride | 2024-06-25

REPOSITORIES: Pride

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			Action	DRS
	DesignPRIDE-Gretchen022023.xlsx	Xlsx
	E0750FD.msf	Msf
	E0750FD.raw	Raw
	E0751FD.msf	Msf
	E0751FD.raw	Raw

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