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Rrp6-mediated heterochromatin surveillance secures antigenic variation and sexual commitment of human malaria parasites

ABSTRACT: Rrp6-mediated heterochromatin surveillance secures antigenic variation and sexual commitment of human malaria parasites

PROVIDER: PRJNA550424 | ENA |

REPOSITORIES: ENA

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Rrp6-mediated heterochromatin surveillance secures antigenic variation and sexual commitment of human malaria parasites

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GDV1 triggers sexual conversion and differentiation in malaria parasites by antagonizing HP1-dependent gene silencing

Project description:Malaria is caused by Plasmodium parasites that proliferate through iterative cycles of intra-erythrocytic replication. During each cycle a small number of parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)-dependent silencing of ap2-g prevents sexual conversion and secures proliferation. Here, we identify gametocyte development 1 (GDV1) as the first upstream activator of the sexual differentiation pathway in P. falciparum. Induction of GDV1 expression is sufficient to activate AP2-G expression and sexual differentiation. We found that GDV1 targets heterochromatin and triggers HP1 eviction preferentially at ap2-g and other gametocyte-specific genes. We further demonstrate that GDV1-dependent activation of ap2-g is controlled via a gdv1 antisense RNA. In summary, we identify GDV1 as an unprecedented cell fate decision factor that induces sexual differentiation by antagonizing HP1-dependent gene silencing.

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