RNA polymerase III is involved in regulatingPlasmodium falciparumvirulence

Abstract

SummaryMalaria pathogenesis is linked to parasite sequestration in critical target organs and is regulated seasonally in malaria-endemic regions, suggesting environmental sensing might regulate disease severity. How this occurs at the molecular level and the contributing host and parasite factors remain unclear. Here, we report thatP. falciparumRNA polymerase III (RNA Pol III) transcription is downregulated in field isolates from asymptomatic patients. By usingin vitrocultured parasites, we identified an RNA Pol III-dependent mechanism that governs expression of a major virulence factor in response to external stimuli. We establish a link betweenP. falciparumcytoadhesion and a Pol III-transcribed non-coding RNA family. Furthermore, we identifyP. falciparumMaf1 as a critical regulator of Pol III transcription for cellular homeostasis and in adaptive responsive to external stimuli. Our results identify an RNA Pol III-dependent reduction in parasite cytoadherence capacity and link this process to asymptomatic malaria infection.