Ribosome heterogeneity and specialization of Plasmodium parasites

Malaria remains a major global health burden, causing over 247 million cases and 619,000 deaths in 2021 [1].This disease is caused by eukaryotic, apicomplexan parasites in the species Plasmodium, with the majority of cases caused by Plasmodium falciparum.With drug resistance on the rise, it is crucial to identify and exploit specific and essential features of the parasite.One of these differences is the temporally restricted expression of two types of ribosomal RNAs (rRNAs), the Asexual A-type and Sporozoite S-type.These rRNA types are conserved across Plasmodium species and have contributed to the reemerging acceptance that ribosomes are heterogeneous and can be specialized in their composition and function in eukaryotes [2,3]. HistoricalAU : Pleaseconfirmthatallheadinglevelsarerepresentedcorrectly: support for and against ribosome heterogeneityWhen ribosomes were first discovered in the 1930s to 1950s, scientists acknowledged that they were heterogeneous, noticing differences in the size and shapes of the particles observed with electron microscopy [4].This model was furthered by a hypothesis that described how each ribosome would contain the genetic information needed to translate one protein [5].However, as this hypothesis was disproven and disregarded, so too was the model of ribosome heterogeneity.This shift away from a model of ribosome specialization was supported by the finding that the introduction of foreign bacteriophage RNA into E. coli was translated by the bacterial ribosomes [6].The scientific community accepted that ribosomes were nonspecialized machines that would translate any mRNA into protein.Advances in research methodologies and technologies have enabled more detailed studies of ribosomes, which more clearly showed that ribosomes could be heterogenous in their ribosome protein (RP) composition.These differences in RP composition can be due to the expression of specific RP paralogs in different tissues or organs, such as RPS5A and RPS18A in proliferating tissues of Arabidopsis [7] in the sex organs in both Drosophila [8] and mice [9], and as cells continue to differentiate and develop [10].Additionally, in mice, the incorporation of the RP paralog RPL39L (Ribosomal Protein of the Large ribosomal subunit L39-Like) into the ribosome impacts the velocity of translation [11] by changing the polypeptide exit tunnel size and charge, which helps regulate the folding of a subset of essential, male germ cell-specific proteins required for sperm formation [12].Ribosomes containing RPL10A in developing mice embryos prefer transcripts of members of the canonical Wnt signaling pathway, creating a specialization that is essential for proper mesoderm production during development [13].Furthermore, while the evolutionarily conserved core rRNA maintains a high degree of conservation across species, it was appreciated that eukaryotes had evolved their rRNA sequences to include expansion segments (ESs).These ESs are protrusions from the core