Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine

Area of Science:

• Molecular Biology
• Parasitology
• Structural Biology

Background:

• Apicomplexa are parasites causing significant global disease burden.
• Their reduced mitochondrial genomes pose challenges in understanding mitoribosome function.
• Mitoribosomal RNAs (mt-rRNAs) in Apicomplexa are highly fragmented.

Purpose of the Study:

• To elucidate the assembly and structure of the apicomplexan mitoribosome.
• To identify the components involved in organizing fragmented mt-rRNAs.
• To explore the roles of unique RNA-binding proteins in parasite mitochondria.

Main Methods:

• Cryo-electron microscopy (Cryo-EM) for structural analysis.
• Biochemical assays to study protein-RNA interactions.
• Genetic analysis of nuclear-encoded mitochondrial proteins.

Main Results:

• Over 40 mt-rRNA fragments are assembled using nuclear-encoded proteins.
• Apicetal2/Ethylene Response Factor (AP2/ERF) proteins, originally plant transcription factors, are essential for mitoribosome integrity.
• Lineage-specific RNA-binding proteins (RAP and HPR families) are crucial components.

Conclusions:

• Apicomplexan mitoribosomes utilize repurposed transcription factors and novel RNA-binding proteins for assembly.
• The unique structure highlights parasite-specific adaptations in organellar translation.
• Understanding these mechanisms may lead to new therapeutic strategies against apicomplexan diseases.