Different classes of RNA require distinct Mex67 paralogs for processing and nucleocytoplasmic export in trypanosomes.

Abstract

The nuclear pore complex (NPC) is at the center of nucleocytoplasmic transport as well as many aspects of gene regulation. A series of steps involving the NPC enable the translation of genes to proteins, starting with the initiation of transcription, through quality control and transport through the NPC, to finally the remodeling of ribonucleoprotein (RNA‐protein) complexes on the cytoplasmic face of the NPC. We recently described the architecture of the trypanosome NPC. Notably absent from the cytoplasmic face of the trypanosome NPC are a host of anchored RNA export and remodeling proteins found in the opisthokont (yeast and human) cytoplasmic RNA export platform. This pointed to a significantly different mode of RNA export and processing in trypanosomes. An evolutionarily conserved group of proteins termed nuclear export factors (NXFs) are responsible for the transport of bulk mRNA from the nucleus to the cytoplasm for translation into proteins, as well as aiding ribosomal subunit export. There is a single major nuclear export factor in yeast (Mex67 or NXF1 in metazoa); although metazoans have additional tissue‐specific NXF variants. All variants of NXF form a heterodimer with Nuclear Transport Factor 2 (NTF2)‐Like Export Factor 1 (NXT1 in humans or Mtr2 in yeast), which facilitates NPC localization and translocation. Orthologs of both NXF and NXT have been identified in trypanosomes, termed TbMex67 and TbMtr2 respectively. Our data suggests that there are in fact three Mex67 paralogs in trypanosomes. We provide evidence strongly indicating they have crucial differing functions. As RNA processing and export are highly integrated events, the export pathway is likely an important step in the regulation of gene expression in trypanosomes.Support or Funding InformationNIAID Exploratory/Developmental Research Grant 1R21AI096069 (to MR)NIGMS GM103314 (to BC), GM103511 and GM109824 (to MR and BC);Wellcome Trust grant 082813/Z/07/Z (to MF and MR).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.