Humboldt University Berlin, Molecular Genetics, Berlin, Germany.
Humboldt University, Department of Molecular Parasitology, Berlin, Germany.
Nucleic Acids Res. 2018 Nov 2;46(19):10417-10431. doi: 10.1093/nar/gky710.
Gene expression in mitochondria of Plasmodium falciparum is essential for parasite survival. The molecular mechanisms of Plasmodium organellar gene expression remain poorly understood. This includes the enigmatic assembly of the mitochondrial ribosome from highly fragmented rRNAs. Here, we present the identification of clustered organellar short RNA fragments (cosRNAs) that are possible footprints of RNA-binding proteins (RBPs) in Plasmodium organelles. In plants, RBPs of the pentatricopeptide repeat (PPR) class produce footprints as a consequence of their function in processing organellar RNAs. Intriguingly, many of the Plasmodium cosRNAs overlap with 5'-ends of rRNA fragments. We hypothesize that these are footprints of RBPs involved in assembling the rRNA fragments into a functioning ribosome. A bioinformatics search of the Plasmodium nuclear genome identified a hitherto unrecognized organellar helical-hairpin-repeat protein family that we term heptatricopeptide repeat (HPR) proteins. We demonstrate that selected HPR proteins are targeted to mitochondria in P. berghei and that one of them, PbHPR1, associates with RNA, but not DNA in vitro. A phylogenetic search identified HPR proteins in a wide variety of eukaryotes. We hypothesize that HPR proteins are required for processing and stabilizing RNAs in Apicomplexa and other taxa.
疟原虫线粒体中的基因表达对寄生虫的存活至关重要。然而，疟原虫细胞器基因表达的分子机制仍知之甚少。这包括高度碎片化 rRNA 组装线粒体核糖体的神秘过程。在这里，我们介绍了聚集的细胞器短 RNA 片段（cosRNA）的鉴定，这些片段可能是疟原虫细胞器中 RNA 结合蛋白（RBP）的足迹。在植物中，五肽重复（PPR）类别的 RBP 因其在加工细胞器 RNA 中的功能而产生足迹。有趣的是，许多疟原虫 cosRNA 与 rRNA 片段的 5'-末端重叠。我们假设这些是参与将 rRNA 片段组装成功能核糖体的 RBP 的足迹。对疟原虫核基因组的生物信息学搜索鉴定了一个迄今未被识别的细胞器螺旋-发夹重复蛋白家族，我们称之为七肽重复（HPR）蛋白。我们证明，选定的 HPR 蛋白在 P. berghei 中靶向线粒体，其中一种蛋白 PbHPR1 与体外的 RNA 而非 DNA 结合。系统发育搜索在各种真核生物中鉴定了 HPR 蛋白。我们假设 HPR 蛋白是顶复门生物和其他类群中加工和稳定 RNA 所必需的。
