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Published on: July 22, 2014
Division of labor in trypanosome RNA processing and export through expanded Mex67 paralogs
Samson O Obado1,2, Peter C Fridy2, Eva Hegedűsová3
1Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98101, United States.
Abstract:
In animals and fungi, bulk messenger RNA (mRNA) export to the cytoplasm is mediated by the Mex67/Mtr2 (NXF1/NXT1) heterodimer and driven by an ATP-dependent remodeling machinery on the cytoplasmic side of nuclear pore complexes, the exclusive gateways of nucleocytoplasmic transport. Uniquely, we show that trypanosomes have three distinct Mex67 paralogs (TbMex67, TbMex67b, and TbMex67L); each having a different non-redundant role in ribosomal RNA (rRNA) processing and mRNA export. Specifically, TbMex67 and TbMex67b retain canonical roles in mRNA export, albeit associating with specific mRNA cohorts and differing protein and mRNA interactomes in the vertebrate host and insect vector forms of the parasite. Further, TbMex67 and TbMex67b paralogs associate with the GTPase Ran export machinery, rather than ATP-dependent helicases, demonstrating significant departure in RNA export mechanisms in trypanosomes. In contrast, TbMex67L is not involved in mRNA export but primarily associates with ribosome biogenesis factors. Thus, in trypanosomes Mex67 paralogs have diverse functionalities with implications for evolutionary origins and diversity of the control of gene expression.
Insights
Trypanosomes utilize three distinct Mex67 proteins for RNA export and ribosome processing, diverging from typical mechanisms. These paralogs (TbMex67, TbMex67b, TbMex67L) have unique roles, impacting gene expression control.
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.
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