Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan.
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Proc Natl Acad Sci U S A. 2023 Jul 11;120(28):e2214765120. doi: 10.1073/pnas.2214765120. Epub 2023 Jul 5.
The malaria parasite has a nonphotosynthetic plastid called the apicoplast, which contains its own genome. Regulatory mechanisms for apicoplast gene expression remain poorly understood, despite this organelle being crucial for the parasite life cycle. Here, we identify a nuclear-encoded apicoplast RNA polymerase σ subunit (sigma factor) which, along with the α subunit, appears to mediate apicoplast transcript accumulation. This has a periodicity reminiscent of parasite circadian or developmental control. Expression of the apicoplast subunit gene, , together with apicoplast transcripts, increased in the presence of the blood circadian signaling hormone melatonin. Our data suggest that the host circadian rhythm is integrated with intrinsic parasite cues to coordinate apicoplast genome transcription. This evolutionarily conserved regulatory system might be a future target for malaria treatment.
疟原虫有一种非光合质体,称为顶质体,它包含自己的基因组。尽管这个细胞器对寄生虫的生命周期至关重要,但顶质体基因表达的调节机制仍知之甚少。在这里,我们鉴定了一种核编码的顶质体 RNA 聚合酶 σ 亚基(σ 因子),它与 α 亚基一起,似乎介导了顶质体转录物的积累。这具有类似于寄生虫生物钟或发育控制的周期性。在血液生物钟信号激素褪黑素的存在下,顶质体亚基基因和顶质体转录物的表达增加。我们的数据表明,宿主生物钟节律与内在寄生虫线索相整合,以协调顶质体基因组转录。这个进化上保守的调节系统可能是未来疟疾治疗的一个目标。