A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite
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Updated: Jan 7, 2026

Methods to Investigate the Regulatory Role of Small RNAs and Ribosomal Occupancy of Plasmodium falciparum
Published on: December 4, 2015
Justine E Couble1, Tiziano Vignolini1, Grégory Doré1
1Institut Pasteur, Université Paris Cité, INSERM U1347, G5 Parasite RNA Biology Group, F-75015, Paris, France.
Abstract:
The transmission of the most virulent human malaria parasite, Plasmodium falciparum, relies on its survival in the contrasting environments of the human host and mosquito vector. One of the most fascinating adaptations to this lifestyle is the specific silencing of individual rDNA genes in the human host that are de-repressed following host-to-vector transmission. In this study, we define the epigenetic signatures of rRNA transcription and find that rDNA silencing relies on aerobic glycolysis, the sole energy-generating pathway in the human host. We show that disruption of NAD+ regeneration during lactate fermentation promotes rDNA de-repression and identify the sirtuin histone deacetylase Sir2a as the mediator between fluctuating NAD+ levels and a functional transcriptional outcome. Hence, rDNA activation appears to be coupled to the metabolic state of the parasite as it transitions from aerobic glycolysis to mitochondrial respiration during host-to-vector transmission.
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