HPR Proteins – New Players in Apicomplexa Organellar RNA Metabolism
Plasmodium cells depend on two DNA-bearing organelles, the apicoplasts and mitochondria. Gene expression in these organelles is essential for parasite survival, with antibiotics targeting gene expression in the apicoplast and mitochondrion serving as potent antimalarials. The details of Plasmodium organellar gene expression, i.e. the individual expression steps as well as the underlying factors, are poorly understood. This includes the enigmatic assembly of the ribosome from the highly fragmented rRNAs in the mitochondrion. We have recently found short non-coding RNA fragments that are possible footprints of RNA binding proteins in Plasmodium organelles. In plants, RBPs of the PPR class produce footprints as a result of their job in processing organellar RNAs. Intriguingly, many of the Plasmodium organellar short RNAs (sRNAs) overlap with 5’ ends of rRNA fragments. We hypothesize that these are footprints of RBPs involved in puzzling together the rRNA fragments into a functioning ribosome. A bioinformatics search of the Plasmodium nuclear genome identified a hitherto undescribed family of organellar helical hairpin repeat protein family that we term heptatricopeptide repeat (HPR) proteins and that bear striking resemblance to plant proteins involved in organellar RNA processing. These proteins are predicted to be imported into the Plasmodium organelles, which we have confirmed for selected candidates. We demonstrate RNA binding by pull-down analysis. A phylogenetic search identified HPR proteins in a wide variety of heterotrophic organisms. We hypothesize that HPR proteins are required for processing and stabilizing RNAs in Apicomplexa and beyond.