Division of labor in trypanosome RNA processing and export through expanded Mex67 paralogs
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.
Authors
- Wenzhu Zhang (ORCID: https://orcid.org/0009-0001-3154-871X)
- Zdeněk Paris (ORCID: https://orcid.org/0000-0003-1019-7719)
- Samson O. Obado (ORCID: https://orcid.org/0000-0003-3161-0218)
- Bryan C. Jensen (ORCID: https://orcid.org/0000-0002-4281-6513)
- Peter C. Fridy (ORCID: https://orcid.org/0000-0002-8208-9154)
- Michael P. Rout (ORCID: https://orcid.org/0000-0003-2010-706X)
- Eva Hegedűsová (ORCID: https://orcid.org/0000-0002-6266-1811)
- Marc Brillantes
- Trevor van Eeuwen (ORCID: https://orcid.org/0000-0003-0549-1702)
- Milana E. Stein (ORCID: https://orcid.org/0000-0001-6540-4389)
- Brian T. Chait (ORCID: https://orcid.org/0000-0003-3524-557X)
- Lucy Glover (ORCID: https://orcid.org/0000-0001-7191-6890)
- M. A. S. Field
- Connor Chung
Institutions
- Center for Infectious Disease Research (US)
- Infectious Disease Research Institute (US)
- Inserm (FR)
- Institut Pasteur (FR)
- University of Dundee (GB)
- Institute of Parasitology of the Slovak Academy of Sciences (SK)
- Rockefeller University (US)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-12-05
- DOI
- https://doi.org/10.1093/nar/gkaf1443
- Primary Topic
- Trypanosoma species research and implications
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- University of Dundee
- Wellcome Trust
- Ministerstvo Školství, Mládeže a Tělovýchovy
- Grantová Agentura České Republiky
- National Institutes of Health
- European Regional Development Fund
- European Social Fund