title: Defects in THO/TREX-2 function cause accumulation of novel cytoplasmic mRNP granules that can be cleared by autophagy.
abstract: The nuclear THO and TREX-2 complexes are implicated in several steps of nuclear mRNP biogenesis, including transcription, 3' end processing and export. In a recent genomic microscopy screen in Saccharomyces cerevisiae for mutants with constitutive stress granules, we identified that absence of THO and TREX-2 complex subunits leads to the accumulation of Pab1-GFP in cytoplasmic foci. We now show that these THO/TREX-2 mutant induced foci ("TT foci") are not stress granules but instead are a mRNP granule containing poly(A)(+) mRNA, some mRNP components also found in stress granules, as well several proteins involved in mRNA 3' end processing and export not normally seen in stress granules. In addition, TT foci are resistant to cycloheximide-induced disassembly, suggesting the presence of mRNPs impaired for entry into translation. THO mutants also exhibit defects in normal stress granule assembly. Finally, our data also suggest that TT foci are targeted by autophagy. These observations argue that defects in nuclear THO and TREX-2 complexes can affect cytoplasmic mRNP function by producing aberrant mRNPs that are exported to cytosol, where they accumulate in TT foci and ultimately can be cleared by autophagy. This identifies a novel mechanism of quality control for aberrant mRNPs assembled in the nucleus.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Nichole
authors.initials: N
authors.lastname: Eshleman
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Kaitlyn
authors.initials: K
authors.lastname: McGrath
authors.affiliation: Department of Chemistry and Biochemistry and Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, Colorado 80303, USA.
authors.forename: Roy
authors.initials: R
authors.lastname: Parker
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: J Ross
authors.initials: JR
authors.lastname: Buchan
mesh_terms: D001343:Autophagy; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*
chemical_list: D012261:Ribonucleoproteins; D003513:Cycloheximide
keywords: THO complex; TREX-2 complex; mRNA; stress granules; translation