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A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite

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...

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Main Authors: Couble, Justine E. (Author) , Vignolini, Tiziano (Author) , Doré, Grégory (Author) , Mussgnug, Selina (Author) , Lombard, Bérangère (Author) , Richard, Michael (Author) , Loew, Damarys (Author) , Büttner, Michael (Author) , Duenas-Sánchez, Rafael (Author) , Poschet, Gernot (Author) , Bryant, Jessica M. (Author) , Baumgarten, Sebastian (Author)
Format: Article (Journal)
Language:English
Published: 2026
In: Nature Communications
Year: 2026, Volume: 17, Pages: 1-18
ISSN:2041-1723
DOI:10.1038/s41467-025-67522-w
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-67522-w
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-67522-w
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Author Notes:Justine E. Couble, Tiziano Vignolini, Grégory Doré, Selina Mussgnug, Bérangère Lombard, Michael Richard, Damarys Loew, Michael Büttner, Rafael Dueñas-Sánchez, Gernot Poschet, Jessica M. Bryant & Sebastian Baumgarten
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Summary: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.
Item Description:Online veröffentlicht: 19. Dezember 2025
Gesehen am 16.03.2026
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-67522-w

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