Division of labor in trypanosome RNA processing and export through expanded Mex67 paralogs

Area of Science:

• Molecular Biology
• Cell Biology
• Parasitology

Background:

• Bulk messenger RNA (mRNA) export in animals and fungi relies on the Mex67/Mtr2 (NXF1/NXT1) complex and ATP-dependent machinery.
• Nuclear pore complexes are the sole gateways for nucleocytoplasmic transport.

Purpose of the Study:

• To investigate the roles of Mex67 paralogs in trypanosome RNA export and ribosome biogenesis.
• To understand the unique mechanisms of nucleocytoplasmic transport in trypanosomes.

Main Methods:

• Identification and characterization of three distinct Mex67 paralogs in trypanosomes (TbMex67, TbMex67b, TbMex67L).
• Analysis of protein and mRNA interactomes in different life stages of the parasite.
• Investigation of associations with export machinery, including GTPase Ran and ATP-dependent helicases.

Main Results:

• Each trypanosome Mex67 paralog (TbMex67, TbMex67b, TbMex67L) has a non-redundant function.
• TbMex67 and TbMex67b are involved in mRNA export, interacting with specific mRNA subsets and exhibiting distinct interactomes.
• TbMex67L is primarily involved in ribosome biogenesis, not mRNA export.
• TbMex67 and TbMex67b associate with the Ran GTPase export machinery, unlike the ATP-dependent helicases seen in other eukaryotes.

Conclusions:

• Trypanosomes possess a unique RNA export system employing three Mex67 paralogs with specialized functions.
• The reliance on Ran GTPase machinery for mRNA export represents a significant divergence from established eukaryotic pathways.
• These findings offer insights into the evolution and diversity of gene expression regulation in eukaryotes.