Ribosomal Architecture and rRNA Modification Landscape in the Tick-Borne Parasite Babesia divergens

Area of Science:

• Molecular Biology
• Parasitology
• Structural Biology

Background:

• Babesia is a tick-borne parasite causing diseases with increasing global reach.
• Gene expression regulation is vital for Babesia's complex life cycle.
• Structural data of translation machinery can inform antiparasitic drug development.

Purpose of the Study:

• To determine the high-resolution cryo-EM ribosome structure of Babesia divergens.
• To identify and characterize novel rRNA modifications in Babesia.
• To explore potential therapeutic targets for babesiosis.

Main Methods:

• Cryo-electron microscopy (cryo-EM) for ribosome structure determination.
• Nanopore sequencing for comprehensive identification of rRNA modifications.
• High-resolution density map analysis.

Main Results:

• Reported cryo-EM ribosome structures of Babesia divergens at 2.6 Å resolution.
• Identified novel rRNA modifications, some previously unreported, using nanopore sequencing and cryo-EM data.
• Atomic resolution (1.7 Å) analysis revealed details of ribosome structure, including associated tRNAs, mRNA fragments, and RACK1.

Conclusions:

• The Babesia divergens ribosome structure provides atomic-level insights into translation regulation.
• Newly identified rRNA modifications, particularly in reduced expansion segments and essential sites, present potential therapeutic targets.
• This research opens new avenues for developing treatments against babesiosis.