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Molecular and Functional Dissection of Distinct mRNA Export Pathways
Author(s) -
Obado Samson,
Field Mark,
Chat Brian,
Rout Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.627.8
Subject(s) - biology , microbiology and biotechnology , messenger rna , directionality , p bodies , nuclear export signal , small gtpase , rna binding protein , ran , gene , rna , cytoplasm , gtpase , gene expression , genetics , cell nucleus , signal transduction , translation (biology)
The major cellular mRNA export factor Mex67/NXF1 (yeast/vertebrates), together with its partner Mtr2/NXT1, transport mRNAs through the nuclear pore complex (NPC) to the cytoplasm. In most eukaryotes, Mex67/NXF1 exists as a single protein, although in metazoa (including humans) additional tissue‐specific isoforms of NXF1 exist. These paralogs may provide an additional level of tissue‐specific gene control, yet their function has been difficult to separate from the many other levels of gene control exercised by metazoan cells. This mRNA export is dependent on an ATP‐dependent remodeling machinery for its energy and directionality, in contrast to virtually all other nucleocytoplasmic transport pathways, which instead utilize the GTPase Ran. We have discovered that the unicellular protozoan, Trypanosoma , has two very distinct paralogs of Mex67 with differing roles in mRNA export. Control of mRNA levels in trypanosomes is almost exclusively post‐transcriptional, thus potentially positioning RNA export as a major mechanism for controlling gene expression. Indeed our results indicate that the two Mex67 paralogs, termed TbMex67 and TbMex67b, are life cycle specific, playing different roles in the mammalian bloodstream form of the organism versus the insect procyclic form. In addition to extreme reliance on post‐transcriptional gene regulation, we have previously shown that the trypanosomatid NPCs lacks the entire mRNA export platform and associating ATP‐dependent machinery that is required to drive and provide directionality to mRNA export in yeast and metazoans. Instead, our results strongly indicate that mRNA export in these organisms is dependent for both directionality and energy on the Ran GTPase system, providing a new perspective on how Ran can be remodeled to mediate an alternate directional transport pathway across the NPC. Support or Funding Information NIAID 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).A comparison of the control of gene regulation in opisthokonts (yeast and humans) versus trypanosomes Gene regulation in trypanosomes is posttranscriptional, laying special emphasis on the nuclear pore complex and RNA export as a fundamental part of the regulatory process.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .