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.

Center for Global Infectious Disease Research Seattle Children's Research Institute Seattle WA 98101 United States

Institute of Parasitology Biology Centre Czech Academy of Sciences Branišovská 1160 31 370 05 České Budějovice Czech Republic

Laboratory of Cellular and Structural Biology The Rockefeller University 1230 York Avenue New York NY 10065 United States

Laboratory of Mass Spectrometry and Gaseous Ion Chemistry The Rockefeller University 1230 York Avenue New York NY 10065 United States

School of Life Sciences University of Dundee Dow Street Dundee DD1 5EH United Kingdom

Trypanosome Molecular Biology Unit Institut Pasteur Université Paris Cite INSERM U1347 25 28 Rue du Dr Roux 75015 Paris France

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