A metabolism-chromatin axis promotes differential ribosomal RNA transcription in the human malaria parasite.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41419483.
- Also identified by DOI 10.1038/s41467-025-67522-w and PMC identifier 12824157.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> regeneration during lactate fermentation promotes rDNA de-repression and identify the sirtuin histone deacetylase Sir2a as the mediator between fluctuating NAD<sup>+</sup> 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.
Medical subject headings
- Plasmodium falciparum
- RNA, Ribosomal
- Chromatin
- Transcription, Genetic
- Malaria, Falciparum