Differences in structure and hibernation mechanism highlight diversification of the microsporidian ribosome

Abstract

Assembling and powering ribosomes are energy-intensive processes requiring fine-tuned cellular control mechanisms. In organisms operating under strict nutrient limitations, such as pathogenic microsporidia, conservation of energy via ribosomal hibernation and recycling is critical. The mechanisms by which hibernation is achieved in microsporidia, however, remain poorly understood. Here, we present the cryo–electron microscopy structure of the ribosome from Paranosema locustae spores, bound by the conserved eukaryotic hibernation and recycling factor Lso2. The microsporidian Lso2 homolog adopts a V-shaped conformation to bridge the mRNA decoding site and the large subunit tRNA binding sites, providing a reversible ribosome inactivation mechanism. Although microsporidian ribosomes are highly compacted, the P. locustae ribosome retains several rRNA segments absent in other microsporidia, and represents an intermediate state of rRNA reduction. In one case, the near complete reduction of an expansion segment has resulted in a single bound nucleotide, which may act as an architectural co-factor to stabilize a protein–protein interface. The presented structure highlights the reductive evolution in these emerging pathogens and sheds light on a conserved mechanism for eukaryotic ribosome hibernation.

Adaptation to genome decay in the structure of the smallest eukaryotic ribosome

“…Compared to the previously determined structures of V. necatrix and P. locustae ribosomes (both structures represent the same family of Nosematidae microsporidians and are very similar to each other) 31 , 32 , E. cuniculi ribosomes underwent further degeneration of numerous rRNA and proteins segments (Supplementary Figs. 4 – 6 ).…”

“…E. cuniculi is a fungi-like organism, which belongs to the group of parasites microsporidia, which possess anomalously small eukaryotic genomes and are therefore used as model organisms to study genome decay 25 – 30 . Recently, cryo-EM structures of ribosomes were determined for microsporidians with moderately reduced genomes, Paranosema locustae and Vairimorpha necatrix 31 , 32 (~3.2 Mb genomes). These structures showed that the loss of some rRNA expansions is compensated by evolving new contacts between adjacent ribosomal proteins or by the acquisition of a new ribosomal protein, msL1 31 , 32 .…”

“…Recently, cryo-EM structures of ribosomes were determined for microsporidians with moderately reduced genomes, Paranosema locustae and Vairimorpha necatrix 31 , 32 (~3.2 Mb genomes). These structures showed that the loss of some rRNA expansions is compensated by evolving new contacts between adjacent ribosomal proteins or by the acquisition of a new ribosomal protein, msL1 31 , 32 . Encephalitozoon species (~2.5 Mb genomes), along with their closest relatives Ordospora , show the ultimate degree of genome reduction in eukaryotes—they have less than 2,000 protein-coding genes and their ribosomes were predicted to lack not only rRNA expansion segments (rRNA segments that distinguish eukaryotic ribosomes from bacterial ribosomes) but also four ribosomal proteins due to the absence of their homologs in the E. cuniculi genome 26 – 28 .…”

Hibernation-Promoting Factor Sequesters Staphylococcus aureus Ribosomes to Antagonize RNase R-Mediated Nucleolytic Degradation

“…A loss of function of Dis3L proteins is linked to many human diseases ( 62 , 81 ). Hibernating 80S ribosomes are relatively stable ( 6 , 7 , 19 ), and it remains to be determined whether they are protected by preclusion of the action of Dis3L exonucleases and known ribosome degradation pathways such as the ubiquitin-proteasome system and ribophagy ( 82 ). Our discovery fills the knowledge gap between ribosome hibernation and turnover and may delineate general principles of RNase R function in all kingdoms of life.…”

“…The mammalian equivalent of 100S, a dimer of 80S monomers (110 complex), has only been observed in tumor cells under nutrient starvation ( 18 ). Adding to the dissimilarity, eukaryotic hibernation factors (Lso2/CCDC124 and Stm1/SERBP1) clamp the 40S and 60S subunits together to form an inactive 80S complex ( 6 , 7 , 19 ).…”