title: NMD3 regulates both mRNA and rRNA nuclear export in African trypanosomes via an XPOI-linked pathway.
abstract: Trypanosomes mostly regulate gene expression through post-transcriptional mechanisms, particularly mRNA stability. However, much mRNA degradation is cytoplasmic such that mRNA nuclear export must represent an important level of regulation. Ribosomal RNAs must also be exported from the nucleus and the trypanosome orthologue of NMD3 has been confirmed to be involved in rRNA processing and export, matching its function in other organisms. Surprisingly, we found that TbNMD3 depletion also generates mRNA accumulation of procyclin-associated genes (PAGs), these being co-transcribed by RNA polymerase I with the procyclin surface antigen genes expressed on trypanosome insect forms. By whole transcriptome RNA-seq analysis of TbNMD3-depleted cells we confirm the regulation of the PAG transcripts by TbNMD3 and using reporter constructs reveal that PAG1 regulation is mediated by its 5'UTR. Dissection of the mechanism of regulation demonstrates that it is not dependent upon translational inhibition mediated by TbNMD3 depletion nor enhanced transcription. However, depletion of the nuclear export factors XPO1 or MEX67 recapitulates the effects of TbNMD3 depletion on PAG mRNAs and mRNAs accumulated in the nucleus of TbNMD3-depleted cells. These results invoke a novel RNA regulatory mechanism involving the NMD3-dependent nuclear export of mRNA cargos, suggesting a shared platform for mRNA and rRNA export.
authors: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Kings Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
authors: Melanie
authors: M
authors: Bühlmann
authors: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Kings Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK Centre for Immunology and Infection, Department of Biology, University of York, YO10 5DD, UK.
authors: Pegine
authors: P
authors: Walrad
authors: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Kings Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
authors: Eva
authors: E
authors: Rico
authors: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Kings Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
authors: Alasdair
authors: A
authors: Ivens
authors: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Kings Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
authors: Paul
authors: P
authors: Capewell
authors: Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland.
authors: Arunasalam
authors: A
authors: Naguleswaran
authors: Institute of Cell Biology, University of Bern, CH-3012 Bern, Switzerland.
authors: Isabel
authors: I
authors: Roditi
authors: Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, Kings Buildings, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK keith.matthews@ed.ac.uk.
authors: Keith R
authors: KR
authors: Matthews
mesh_terms: D020121:5' Untranslated Regions; D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism*; D028884:Karyopherins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015533:Transcriptional Activation; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000378:metabolism; D000097606:Exportin 1 Protein
chemical_list: D020121:5' Untranslated Regions; D028884:Karyopherins; D029543:Nucleocytoplasmic Transport Proteins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein