Prof. Lilach Sheiner, Parasitology, University of Glasgow

Mitochondrial ribosomes (mitoribosomes) are essential, and their function of synthesising mitochondrial proteins is universal, including in parasites. A small number of long rRNA molecules typically form the core of mitoribosomes, and crucially these rRNAs are capable of independent folding and of forming all the conserved ribosomal functional domains. However, Apicomplexan mitochondrial genomes predict an extremely fragmented rRNA with molecules that are too short to independently form functional ribosomal domains. Here we used structural and reverse genetic approaches to decipher how the highly fragmented rRNA forms a functional ribosome.

We report the cryoEM structure of the Toxoplasma gondii mitoribosome, revealing several novel ribosomal features that enable this remarkably “shuttered” rRNA core to perform its critical function. We found extensive repurposing and re-use of protein-domains and of RNA molecules as a signature feature of apicomplexan, and likely myzozoan, mitoribosomes. One of the examples include the integration of several proteins with transcription factor folds, including AP2 family members that effectively replace conserved and critical ribosomal domains. In another example, proteins with RNA binding domains play a key role in enabling the integration of short rRNA molecules into the structure.

Our study reveals new mechanisms of adaptation for fragmentation of the ribosomal RNA core, with broad implication on ribosome evolution, and with a potential to inform apicomplexan drug discovery.