Work

A trypanosome-specific complex mediates late-stage processing of cytosolic LSU rRNA

Year: 2025

Type: article

Abstract: Unlike most eukaryotes, Trypanosoma brucei processes its cytosolic large subunit (LSU) RNA into six fragments. The factors responsible for these processing events were previously unknown. Here, we identify TbLrRP1 and TbLrRP2 as essential components of this trypanosome-specific LSU RNA processing pathway. Each contains a single transmembrane domain and localizes to the ER membrane and the nuclear envelope, forming a heterodimeric complex. Depletion of either protein disrupts LSU RNA processing, causing accumulation of unprocessed intermediates that are incorporated into translationally active cytosolic polysomes. This disruption impairs, but does not fully halt, growth of both procyclic and bloodstream form trypanosomes. The nuclease-related domain (NERD) of TbLrRP2 is essential for LSU RNA processing. Intriguingly, NERD-containing proteins were predicted to have DNase activity; however, our results suggest that the NERD of TbLrRP2 is a ribonuclease. In contrast, the DEDDh domain of TbLrRP1 is dispensable for LSU RNA processing, indicating it may have a scaffolding role. Both proteins require their transmembrane domains for full functionality. Our findings reveal a lineage-specific processing complex acting at a late stage of LSU RNA maturation, highlighting the unique adaptations of trypanosomal cytosolic ribosome biogenesis.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkaf1327

Authors: Simona Amodeo, Mauro Fischli, Silke Oeljeklaus, Salvatore Calderaro, Bettina Warscheid, André Schneider

Institutions: University of Bern, University of Würzburg

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992