The RNA-binding protein Puf1 functions in the maintenance of gametocytes in Plasmodium falciparum

Translation control plays an important role in the regulation of gene expression in the malaria parasite Plasmodium falciparum, especially in transition stages between the vertebrate host and mosquito vector. Here, we determined the function of the Puf-family member Puf1 (denoted as PfPuf1 for the P. falciparum protein) during P. falciparum sexual development. We show that PfPuf1 was expressed in all gametocyte stages and at higher levels in female gametocytes. PfPuf1 disruption did not interfere with the asexual erythrocyte cycle of the parasite but resulted in an approximately tenfold decrease of mature gametocytes. In the PfPuf1-disrupted lines, gametocytes appeared normal before stage III but subsequently exhibited a sharp decline in gametocytemia. This was accompanied by a concomitant accumulation of dead and dying late-stage gametocytes, which retained normal gross morphology. In addition, significantly more female gametocytes were lost in the PfPuf1-disrupted lines during development, resulting in a reversed male-to-female sex ratio. These results indicate that PfPuf1 is important for the differentiation and maintenance of gametocytes, especially female gametocytes.